CN111511392A - 用于治疗和/或预防肺癌的免疫治疗方法 - Google Patents
用于治疗和/或预防肺癌的免疫治疗方法 Download PDFInfo
- Publication number
- CN111511392A CN111511392A CN201880083511.0A CN201880083511A CN111511392A CN 111511392 A CN111511392 A CN 111511392A CN 201880083511 A CN201880083511 A CN 201880083511A CN 111511392 A CN111511392 A CN 111511392A
- Authority
- CN
- China
- Prior art keywords
- seq
- seqid
- leu
- immunogenic
- amino acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 208000020816 lung neoplasm Diseases 0.000 title claims abstract description 70
- 206010058467 Lung neoplasm malignant Diseases 0.000 title claims abstract description 67
- 201000005202 lung cancer Diseases 0.000 title claims abstract description 67
- 238000011282 treatment Methods 0.000 title claims abstract description 30
- 238000000034 method Methods 0.000 title claims description 81
- 230000001024 immunotherapeutic effect Effects 0.000 title description 5
- 230000002265 prevention Effects 0.000 title description 3
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 253
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 211
- 229920001184 polypeptide Polymers 0.000 claims abstract description 143
- 230000002163 immunogen Effects 0.000 claims abstract description 108
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 95
- 210000004340 zona pellucida Anatomy 0.000 claims abstract description 92
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 89
- 210000004027 cell Anatomy 0.000 claims abstract description 65
- 239000000203 mixture Substances 0.000 claims abstract description 49
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 39
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 23
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 20
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 20
- 206010027476 Metastases Diseases 0.000 claims abstract description 19
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 13
- 238000003745 diagnosis Methods 0.000 claims abstract description 9
- 108091008874 T cell receptors Proteins 0.000 claims abstract description 4
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims abstract description 4
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 67
- 239000012634 fragment Substances 0.000 claims description 44
- 150000001413 amino acids Chemical class 0.000 claims description 28
- 230000014509 gene expression Effects 0.000 claims description 28
- 239000002671 adjuvant Substances 0.000 claims description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims description 22
- 210000004443 dendritic cell Anatomy 0.000 claims description 15
- 230000009401 metastasis Effects 0.000 claims description 14
- 238000002560 therapeutic procedure Methods 0.000 claims description 12
- 210000001165 lymph node Anatomy 0.000 claims description 11
- 238000007920 subcutaneous administration Methods 0.000 claims description 11
- 210000000612 antigen-presenting cell Anatomy 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 238000011503 in vivo imaging Methods 0.000 claims description 8
- 206010027458 Metastases to lung Diseases 0.000 claims description 7
- 239000000556 agonist Substances 0.000 claims description 7
- 238000007912 intraperitoneal administration Methods 0.000 claims description 7
- 108020004414 DNA Proteins 0.000 claims description 6
- 238000002512 chemotherapy Methods 0.000 claims description 6
- 230000002519 immonomodulatory effect Effects 0.000 claims description 6
- 238000007918 intramuscular administration Methods 0.000 claims description 6
- 238000002626 targeted therapy Methods 0.000 claims description 6
- 102000004127 Cytokines Human genes 0.000 claims description 5
- 108090000695 Cytokines Proteins 0.000 claims description 5
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 claims description 5
- 239000012216 imaging agent Substances 0.000 claims description 5
- 238000011321 prophylaxis Methods 0.000 claims description 5
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 claims description 4
- 238000001959 radiotherapy Methods 0.000 claims description 4
- 230000000735 allogeneic effect Effects 0.000 claims description 3
- 210000005260 human cell Anatomy 0.000 claims description 3
- 230000002601 intratumoral effect Effects 0.000 claims description 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 3
- 238000001356 surgical procedure Methods 0.000 claims description 3
- 230000008685 targeting Effects 0.000 claims description 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 3
- 102000053602 DNA Human genes 0.000 claims description 2
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 claims description 2
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 claims description 2
- 238000011260 co-administration Methods 0.000 claims description 2
- 239000000824 cytostatic agent Substances 0.000 claims description 2
- 239000002254 cytotoxic agent Substances 0.000 claims description 2
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 claims description 2
- 230000001506 immunosuppresive effect Effects 0.000 claims description 2
- 230000000813 microbial effect Effects 0.000 claims description 2
- 102000003298 tumor necrosis factor receptor Human genes 0.000 claims description 2
- 241000186781 Listeria Species 0.000 claims 1
- 229940127089 cytotoxic agent Drugs 0.000 claims 1
- 231100000599 cytotoxic agent Toxicity 0.000 claims 1
- 210000000581 natural killer T-cell Anatomy 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 59
- 230000027455 binding Effects 0.000 abstract description 48
- 102000036639 antigens Human genes 0.000 abstract description 30
- 108091007433 antigens Proteins 0.000 abstract description 30
- 239000000427 antigen Substances 0.000 abstract description 28
- 201000011510 cancer Diseases 0.000 abstract description 24
- 230000024932 T cell mediated immunity Effects 0.000 abstract description 6
- 101000976442 Homo sapiens Zona pellucida sperm-binding protein 3 Proteins 0.000 abstract description 4
- 230000000890 antigenic effect Effects 0.000 abstract description 3
- 230000003053 immunization Effects 0.000 description 28
- 238000002649 immunization Methods 0.000 description 28
- 102000043131 MHC class II family Human genes 0.000 description 24
- 108091054438 MHC class II family Proteins 0.000 description 24
- 108091054437 MHC class I family Proteins 0.000 description 23
- 210000001519 tissue Anatomy 0.000 description 23
- 102000043129 MHC class I family Human genes 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 108090000288 Glycoproteins Proteins 0.000 description 13
- 239000012153 distilled water Substances 0.000 description 13
- 102000003886 Glycoproteins Human genes 0.000 description 12
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 12
- 238000003364 immunohistochemistry Methods 0.000 description 12
- 239000003446 ligand Substances 0.000 description 12
- 238000010186 staining Methods 0.000 description 12
- 239000003814 drug Substances 0.000 description 11
- 229940127121 immunoconjugate Drugs 0.000 description 11
- 108010050848 glycylleucine Proteins 0.000 description 10
- 230000028993 immune response Effects 0.000 description 10
- 238000002347 injection Methods 0.000 description 9
- 239000007924 injection Substances 0.000 description 9
- 210000004072 lung Anatomy 0.000 description 9
- 210000000287 oocyte Anatomy 0.000 description 9
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 8
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 8
- 108010051242 phenylalanylserine Proteins 0.000 description 8
- 230000004044 response Effects 0.000 description 8
- 239000011534 wash buffer Substances 0.000 description 8
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 7
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- 238000013019 agitation Methods 0.000 description 7
- 230000002068 genetic effect Effects 0.000 description 7
- 108020004999 messenger RNA Proteins 0.000 description 7
- 230000004048 modification Effects 0.000 description 7
- 238000012986 modification Methods 0.000 description 7
- 108010026333 seryl-proline Proteins 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 241000282412 Homo Species 0.000 description 6
- 241000699660 Mus musculus Species 0.000 description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 6
- 239000006180 TBST buffer Substances 0.000 description 6
- KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 6
- 238000003018 immunoassay Methods 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 108010057821 leucylproline Proteins 0.000 description 6
- 108010017391 lysylvaline Proteins 0.000 description 6
- 108010053725 prolylvaline Proteins 0.000 description 6
- 210000000952 spleen Anatomy 0.000 description 6
- 206010041823 squamous cell carcinoma Diseases 0.000 description 6
- 108010061238 threonyl-glycine Proteins 0.000 description 6
- 238000011830 transgenic mouse model Methods 0.000 description 6
- 239000003656 tris buffered saline Substances 0.000 description 6
- 239000008096 xylene Substances 0.000 description 6
- 108700028369 Alleles Proteins 0.000 description 5
- VUGWHBXPMAHEGZ-SRVKXCTJSA-N Arg-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCCN=C(N)N VUGWHBXPMAHEGZ-SRVKXCTJSA-N 0.000 description 5
- BUVMZWZNWMKASN-QEJZJMRPSA-N Glu-Asn-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)N)C(O)=O)=CNC2=C1 BUVMZWZNWMKASN-QEJZJMRPSA-N 0.000 description 5
- 102100034535 Histone H3.1 Human genes 0.000 description 5
- 101001067844 Homo sapiens Histone H3.1 Proteins 0.000 description 5
- PMGDADKJMCOXHX-UHFFFAOYSA-N L-Arginyl-L-glutamin-acetat Natural products NC(=N)NCCCC(N)C(=O)NC(CCC(N)=O)C(O)=O PMGDADKJMCOXHX-UHFFFAOYSA-N 0.000 description 5
- BJWKOATWNQJPSK-SRVKXCTJSA-N Leu-Met-Glu Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N BJWKOATWNQJPSK-SRVKXCTJSA-N 0.000 description 5
- ODRREERHVHMIPT-OEAJRASXSA-N Leu-Thr-Phe Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ODRREERHVHMIPT-OEAJRASXSA-N 0.000 description 5
- YTILBRIUASDGBL-BZSNNMDCSA-N Phe-Leu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CC=CC=C1 YTILBRIUASDGBL-BZSNNMDCSA-N 0.000 description 5
- 229920001213 Polysorbate 20 Polymers 0.000 description 5
- 108010076504 Protein Sorting Signals Proteins 0.000 description 5
- VWQVUPCCIRVNHF-OUBTZVSYSA-N Yttrium-90 Chemical compound [90Y] VWQVUPCCIRVNHF-OUBTZVSYSA-N 0.000 description 5
- 230000010056 antibody-dependent cellular cytotoxicity Effects 0.000 description 5
- 230000004540 complement-dependent cytotoxicity Effects 0.000 description 5
- 238000012217 deletion Methods 0.000 description 5
- 230000037430 deletion Effects 0.000 description 5
- -1 deletions (e.g. Chemical class 0.000 description 5
- 239000003599 detergent Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000012636 effector Substances 0.000 description 5
- 108010078144 glutaminyl-glycine Proteins 0.000 description 5
- 108010049041 glutamylalanine Proteins 0.000 description 5
- 238000007901 in situ hybridization Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 230000001939 inductive effect Effects 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 230000002147 killing effect Effects 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 230000002611 ovarian Effects 0.000 description 5
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 5
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 5
- 239000013641 positive control Substances 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- BRPMXFSTKXXNHF-IUCAKERBSA-N (2s)-1-[2-[[(2s)-pyrrolidine-2-carbonyl]amino]acetyl]pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H]1NCCC1 BRPMXFSTKXXNHF-IUCAKERBSA-N 0.000 description 4
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- RRJOQIBQVZDVCW-SRVKXCTJSA-N Cys-His-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CS)N RRJOQIBQVZDVCW-SRVKXCTJSA-N 0.000 description 4
- WDXLKVQATNEAJQ-BQBZGAKWSA-N Gly-Pro-Asp Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O WDXLKVQATNEAJQ-BQBZGAKWSA-N 0.000 description 4
- XLXPYSDGMXTTNQ-UHFFFAOYSA-N Ile-Phe-Leu Natural products CCC(C)C(N)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=CC=C1 XLXPYSDGMXTTNQ-UHFFFAOYSA-N 0.000 description 4
- KYIIALJHAOIAHF-KKUMJFAQSA-N Leu-Leu-His Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 KYIIALJHAOIAHF-KKUMJFAQSA-N 0.000 description 4
- QWWPYKKLXWOITQ-VOAKCMCISA-N Leu-Thr-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC(C)C QWWPYKKLXWOITQ-VOAKCMCISA-N 0.000 description 4
- PHWSCIFNNLLUFJ-NHCYSSNCSA-N Met-Gln-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCSC)N PHWSCIFNNLLUFJ-NHCYSSNCSA-N 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- FUOGXAQMNJMBFG-WPRPVWTQSA-N Pro-Val-Gly Chemical compound OC(=O)CNC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 FUOGXAQMNJMBFG-WPRPVWTQSA-N 0.000 description 4
- MLSQXWSRHURDMF-GARJFASQSA-N Ser-His-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CO)N)C(=O)O MLSQXWSRHURDMF-GARJFASQSA-N 0.000 description 4
- MQUZANJDFOQOBX-SRVKXCTJSA-N Ser-Phe-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(O)=O MQUZANJDFOQOBX-SRVKXCTJSA-N 0.000 description 4
- 206010041067 Small cell lung cancer Diseases 0.000 description 4
- 230000005867 T cell response Effects 0.000 description 4
- ADMHZNPMMVKGJW-BPUTZDHNSA-N Trp-Ser-Arg Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N ADMHZNPMMVKGJW-BPUTZDHNSA-N 0.000 description 4
- BXPOOVDVGWEXDU-WZLNRYEVSA-N Tyr-Ile-Thr Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O BXPOOVDVGWEXDU-WZLNRYEVSA-N 0.000 description 4
- SLLKXDSRVAOREO-KZVJFYERSA-N Val-Ala-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)N)O SLLKXDSRVAOREO-KZVJFYERSA-N 0.000 description 4
- QHDXUYOYTPWCSK-RCOVLWMOSA-N Val-Asp-Gly Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)O)N QHDXUYOYTPWCSK-RCOVLWMOSA-N 0.000 description 4
- SCBITHMBEJNRHC-LSJOCFKGSA-N Val-Asp-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)O)N SCBITHMBEJNRHC-LSJOCFKGSA-N 0.000 description 4
- KISFXYYRKKNLOP-IHRRRGAJSA-N Val-Phe-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)O)N KISFXYYRKKNLOP-IHRRRGAJSA-N 0.000 description 4
- YTNGABPUXFEOGU-SRVKXCTJSA-N Val-Pro-Arg Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(O)=O YTNGABPUXFEOGU-SRVKXCTJSA-N 0.000 description 4
- PZTZYZUTCPZWJH-FXQIFTODSA-N Val-Ser-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)O)N PZTZYZUTCPZWJH-FXQIFTODSA-N 0.000 description 4
- 208000009956 adenocarcinoma Diseases 0.000 description 4
- 230000005888 antibody-dependent cellular phagocytosis Effects 0.000 description 4
- 108010093581 aspartyl-proline Proteins 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 4
- 229960005420 etoposide Drugs 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 230000013595 glycosylation Effects 0.000 description 4
- 238000006206 glycosylation reaction Methods 0.000 description 4
- 210000002443 helper t lymphocyte Anatomy 0.000 description 4
- 108010092114 histidylphenylalanine Proteins 0.000 description 4
- 230000028996 humoral immune response Effects 0.000 description 4
- 230000005847 immunogenicity Effects 0.000 description 4
- 238000011293 immunotherapeutic strategy Methods 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 239000013642 negative control Substances 0.000 description 4
- 108091033319 polynucleotide Proteins 0.000 description 4
- 102000040430 polynucleotide Human genes 0.000 description 4
- 239000002157 polynucleotide Substances 0.000 description 4
- 238000002203 pretreatment Methods 0.000 description 4
- 108010014614 prolyl-glycyl-proline Proteins 0.000 description 4
- 108010070643 prolylglutamic acid Proteins 0.000 description 4
- 238000003127 radioimmunoassay Methods 0.000 description 4
- 208000000587 small cell lung carcinoma Diseases 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 108010071635 tyrosyl-prolyl-arginine Proteins 0.000 description 4
- 238000002255 vaccination Methods 0.000 description 4
- 229960005486 vaccine Drugs 0.000 description 4
- KMGOBAQSCKTBGD-DLOVCJGASA-N Ala-His-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)N)CC1=CN=CN1 KMGOBAQSCKTBGD-DLOVCJGASA-N 0.000 description 3
- WEZNQZHACPSMEF-QEJZJMRPSA-N Ala-Phe-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=CC=C1 WEZNQZHACPSMEF-QEJZJMRPSA-N 0.000 description 3
- NCQMBSJGJMYKCK-ZLUOBGJFSA-N Ala-Ser-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O NCQMBSJGJMYKCK-ZLUOBGJFSA-N 0.000 description 3
- IOFVWPYSRSCWHI-JXUBOQSCSA-N Ala-Thr-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C)N IOFVWPYSRSCWHI-JXUBOQSCSA-N 0.000 description 3
- IASNWHAGGYTEKX-IUCAKERBSA-N Arg-Arg-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(O)=O IASNWHAGGYTEKX-IUCAKERBSA-N 0.000 description 3
- QCTOLCVIGRLMQS-HRCADAONSA-N Arg-Tyr-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O QCTOLCVIGRLMQS-HRCADAONSA-N 0.000 description 3
- KSGAFDTYQPKUAP-GMOBBJLQSA-N Asn-Met-Ile Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O KSGAFDTYQPKUAP-GMOBBJLQSA-N 0.000 description 3
- XHTUGJCAEYOZOR-UBHSHLNASA-N Asn-Ser-Trp Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O XHTUGJCAEYOZOR-UBHSHLNASA-N 0.000 description 3
- ZKAOJVJQGVUIIU-GUBZILKMSA-N Asp-Pro-Arg Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(O)=O ZKAOJVJQGVUIIU-GUBZILKMSA-N 0.000 description 3
- SFJUYBCDQBAYAJ-YDHLFZDLSA-N Asp-Val-Phe Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SFJUYBCDQBAYAJ-YDHLFZDLSA-N 0.000 description 3
- MBILEVLLOHJZMG-FXQIFTODSA-N Cys-Gln-Glu Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CS)N MBILEVLLOHJZMG-FXQIFTODSA-N 0.000 description 3
- OXOQBEVULIBOSH-ZDLURKLDSA-N Cys-Gly-Thr Chemical compound [H]N[C@@H](CS)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O OXOQBEVULIBOSH-ZDLURKLDSA-N 0.000 description 3
- DRNMNLKUUKKPIA-HTUGSXCWSA-N Gln-Phe-Thr Chemical compound C[C@@H](O)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](N)CCC(N)=O)C(O)=O DRNMNLKUUKKPIA-HTUGSXCWSA-N 0.000 description 3
- LGYZYFFDELZWRS-DCAQKATOSA-N Glu-Glu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCC(O)=O LGYZYFFDELZWRS-DCAQKATOSA-N 0.000 description 3
- MXJYXYDREQWUMS-XKBZYTNZSA-N Glu-Thr-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O MXJYXYDREQWUMS-XKBZYTNZSA-N 0.000 description 3
- KQDMENMTYNBWMR-WHFBIAKZSA-N Gly-Asp-Ala Chemical compound [H]NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O KQDMENMTYNBWMR-WHFBIAKZSA-N 0.000 description 3
- CCQOOWAONKGYKQ-BYPYZUCNSA-N Gly-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)CN CCQOOWAONKGYKQ-BYPYZUCNSA-N 0.000 description 3
- JJGBXTYGTKWGAT-YUMQZZPRSA-N Gly-Pro-Glu Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O JJGBXTYGTKWGAT-YUMQZZPRSA-N 0.000 description 3
- IRJWAYCXIYUHQE-WHFBIAKZSA-N Gly-Ser-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)CN IRJWAYCXIYUHQE-WHFBIAKZSA-N 0.000 description 3
- MKIAPEZXQDILRR-YUMQZZPRSA-N Gly-Ser-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)CN MKIAPEZXQDILRR-YUMQZZPRSA-N 0.000 description 3
- LMMPTUVWHCFTOT-GARJFASQSA-N His-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC2=CN=CN2)N)C(=O)O LMMPTUVWHCFTOT-GARJFASQSA-N 0.000 description 3
- SAPLASXFNUYUFE-CQDKDKBSSA-N His-Phe-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC2=CN=CN2)N SAPLASXFNUYUFE-CQDKDKBSSA-N 0.000 description 3
- XVZJRZQIHJMUBG-TUBUOCAGSA-N His-Thr-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC1=CN=CN1)N XVZJRZQIHJMUBG-TUBUOCAGSA-N 0.000 description 3
- QRTVJGKXFSYJGW-KBIXCLLPSA-N Ile-Glu-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CS)C(=O)O)N QRTVJGKXFSYJGW-KBIXCLLPSA-N 0.000 description 3
- URWXDJAEEGBADB-TUBUOCAGSA-N Ile-His-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N URWXDJAEEGBADB-TUBUOCAGSA-N 0.000 description 3
- 108010065920 Insulin Lispro Proteins 0.000 description 3
- 102000008070 Interferon-gamma Human genes 0.000 description 3
- 108010074328 Interferon-gamma Proteins 0.000 description 3
- 241000880493 Leptailurus serval Species 0.000 description 3
- JNDYEOUZBLOVOF-AVGNSLFASA-N Leu-Leu-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O JNDYEOUZBLOVOF-AVGNSLFASA-N 0.000 description 3
- PWPBLZXWFXJFHE-RHYQMDGZSA-N Leu-Pro-Thr Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O PWPBLZXWFXJFHE-RHYQMDGZSA-N 0.000 description 3
- ICYRCNICGBJLGM-HJGDQZAQSA-N Leu-Thr-Asp Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC(O)=O ICYRCNICGBJLGM-HJGDQZAQSA-N 0.000 description 3
- AIMGJYMCTAABEN-GVXVVHGQSA-N Leu-Val-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O AIMGJYMCTAABEN-GVXVVHGQSA-N 0.000 description 3
- 241000186779 Listeria monocytogenes Species 0.000 description 3
- VHFFQUSNFFIZBT-CIUDSAMLSA-N Lys-Ala-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCCCN)N VHFFQUSNFFIZBT-CIUDSAMLSA-N 0.000 description 3
- YTJFXEDRUOQGSP-DCAQKATOSA-N Lys-Pro-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O YTJFXEDRUOQGSP-DCAQKATOSA-N 0.000 description 3
- RIPJMCFGQHGHNP-RHYQMDGZSA-N Lys-Val-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCCN)N)O RIPJMCFGQHGHNP-RHYQMDGZSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- CKAVKDJBSNTJDB-SRVKXCTJSA-N Met-Val-Met Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCSC CKAVKDJBSNTJDB-SRVKXCTJSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 description 3
- BQVUABVGYYSDCJ-UHFFFAOYSA-N Nalpha-L-Leucyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)CC(C)C)C(O)=O)=CNC2=C1 BQVUABVGYYSDCJ-UHFFFAOYSA-N 0.000 description 3
- 229930012538 Paclitaxel Natural products 0.000 description 3
- 108010033276 Peptide Fragments Proteins 0.000 description 3
- 102000007079 Peptide Fragments Human genes 0.000 description 3
- LWPMGKSZPKFKJD-DZKIICNBSA-N Phe-Glu-Val Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O LWPMGKSZPKFKJD-DZKIICNBSA-N 0.000 description 3
- MSSXKZBDKZAHCX-UNQGMJICSA-N Phe-Thr-Val Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O MSSXKZBDKZAHCX-UNQGMJICSA-N 0.000 description 3
- YQHZVYJAGWMHES-ZLUOBGJFSA-N Ser-Ala-Ser Chemical compound OC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O YQHZVYJAGWMHES-ZLUOBGJFSA-N 0.000 description 3
- DOSZISJPMCYEHT-NAKRPEOUSA-N Ser-Ile-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(O)=O DOSZISJPMCYEHT-NAKRPEOUSA-N 0.000 description 3
- QYSFWUIXDFJUDW-DCAQKATOSA-N Ser-Leu-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O QYSFWUIXDFJUDW-DCAQKATOSA-N 0.000 description 3
- HOVLHEKTGVIKAP-WDCWCFNPSA-N Thr-Leu-Gln Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O HOVLHEKTGVIKAP-WDCWCFNPSA-N 0.000 description 3
- GWBWCGITOYODER-YTQUADARSA-N Trp-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)N GWBWCGITOYODER-YTQUADARSA-N 0.000 description 3
- WYOBRXPIZVKNMF-IRXDYDNUSA-N Tyr-Tyr-Gly Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)NCC(O)=O)C1=CC=C(O)C=C1 WYOBRXPIZVKNMF-IRXDYDNUSA-N 0.000 description 3
- HHSILIQTHXABKM-YDHLFZDLSA-N Val-Asp-Phe Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](Cc1ccccc1)C(O)=O HHSILIQTHXABKM-YDHLFZDLSA-N 0.000 description 3
- AGKDVLSDNSTLFA-UMNHJUIQSA-N Val-Gln-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N1CCC[C@@H]1C(=O)O)N AGKDVLSDNSTLFA-UMNHJUIQSA-N 0.000 description 3
- 108010074006 Zona Pellucida Glycoproteins Proteins 0.000 description 3
- 102000008937 Zona Pellucida Glycoproteins Human genes 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 108010005233 alanylglutamic acid Proteins 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 108010060035 arginylproline Proteins 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 229960004562 carboplatin Drugs 0.000 description 3
- 190000008236 carboplatin Chemical compound 0.000 description 3
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 3
- 229960004316 cisplatin Drugs 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 210000000805 cytoplasm Anatomy 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 108010054812 diprotin A Proteins 0.000 description 3
- 108010054813 diprotin B Proteins 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 3
- 108010063718 gamma-glutamylaspartic acid Proteins 0.000 description 3
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 3
- 229960005277 gemcitabine Drugs 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 108010037850 glycylvaline Proteins 0.000 description 3
- 108010025306 histidylleucine Proteins 0.000 description 3
- 102000055956 human ZP3 Human genes 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 229960003130 interferon gamma Drugs 0.000 description 3
- 229960004768 irinotecan Drugs 0.000 description 3
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 3
- 108010044374 isoleucyl-tyrosine Proteins 0.000 description 3
- 108010027338 isoleucylcysteine Proteins 0.000 description 3
- 108010030617 leucyl-phenylalanyl-valine Proteins 0.000 description 3
- 108010091871 leucylmethionine Proteins 0.000 description 3
- 230000003211 malignant effect Effects 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 210000001672 ovary Anatomy 0.000 description 3
- 229960001592 paclitaxel Drugs 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 238000004393 prognosis Methods 0.000 description 3
- 108010090894 prolylleucine Proteins 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- 230000000306 recurrent effect Effects 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 108010071207 serylmethionine Proteins 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 230000009870 specific binding Effects 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 239000008399 tap water Substances 0.000 description 3
- 235000020679 tap water Nutrition 0.000 description 3
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 3
- 229960000303 topotecan Drugs 0.000 description 3
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 3
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 3
- 229960002066 vinorelbine Drugs 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 2
- DKJPOZOEBONHFS-ZLUOBGJFSA-N Ala-Ala-Asp Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC(O)=O DKJPOZOEBONHFS-ZLUOBGJFSA-N 0.000 description 2
- WCBVQNZTOKJWJS-ACZMJKKPSA-N Ala-Cys-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(O)=O WCBVQNZTOKJWJS-ACZMJKKPSA-N 0.000 description 2
- HMRWQTHUDVXMGH-GUBZILKMSA-N Ala-Glu-Lys Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCCN HMRWQTHUDVXMGH-GUBZILKMSA-N 0.000 description 2
- TZDNWXDLYFIFPT-BJDJZHNGSA-N Ala-Ile-Leu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O TZDNWXDLYFIFPT-BJDJZHNGSA-N 0.000 description 2
- YHKANGMVQWRMAP-DCAQKATOSA-N Ala-Leu-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N YHKANGMVQWRMAP-DCAQKATOSA-N 0.000 description 2
- IHMCQESUJVZTKW-UBHSHLNASA-N Ala-Phe-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](C)N)CC1=CC=CC=C1 IHMCQESUJVZTKW-UBHSHLNASA-N 0.000 description 2
- NZGRHTKZFSVPAN-BIIVOSGPSA-N Ala-Ser-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CO)C(=O)N1CCC[C@@H]1C(=O)O)N NZGRHTKZFSVPAN-BIIVOSGPSA-N 0.000 description 2
- OTOXOKCIIQLMFH-KZVJFYERSA-N Arg-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCN=C(N)N OTOXOKCIIQLMFH-KZVJFYERSA-N 0.000 description 2
- DPXDVGDLWJYZBH-GUBZILKMSA-N Arg-Asn-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O DPXDVGDLWJYZBH-GUBZILKMSA-N 0.000 description 2
- JUWQNWXEGDYCIE-YUMQZZPRSA-N Arg-Gln-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(O)=O JUWQNWXEGDYCIE-YUMQZZPRSA-N 0.000 description 2
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 2
- IIAXFBUTKIDDIP-ULQDDVLXSA-N Arg-Leu-Phe Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O IIAXFBUTKIDDIP-ULQDDVLXSA-N 0.000 description 2
- ICRHGPYYXMWHIE-LPEHRKFASA-N Arg-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O ICRHGPYYXMWHIE-LPEHRKFASA-N 0.000 description 2
- VDCIPFYVCICPEC-FXQIFTODSA-N Asn-Arg-Ala Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O VDCIPFYVCICPEC-FXQIFTODSA-N 0.000 description 2
- DJIMLSXHXKWADV-CIUDSAMLSA-N Asn-Leu-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(N)=O DJIMLSXHXKWADV-CIUDSAMLSA-N 0.000 description 2
- KSZHWTRZPOTIGY-AVGNSLFASA-N Asn-Tyr-Gln Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CC(=O)N)N)O KSZHWTRZPOTIGY-AVGNSLFASA-N 0.000 description 2
- PQKSVQSMTHPRIB-ZKWXMUAHSA-N Asn-Val-Ser Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O PQKSVQSMTHPRIB-ZKWXMUAHSA-N 0.000 description 2
- WLKVEEODTPQPLI-ACZMJKKPSA-N Asp-Gln-Asn Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O WLKVEEODTPQPLI-ACZMJKKPSA-N 0.000 description 2
- CMCIMCAQIULNDJ-CIUDSAMLSA-N Asp-His-Cys Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)O)N CMCIMCAQIULNDJ-CIUDSAMLSA-N 0.000 description 2
- CRNKLABLTICXDV-GUBZILKMSA-N Asp-His-Glu Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CC(=O)O)N CRNKLABLTICXDV-GUBZILKMSA-N 0.000 description 2
- LBFYTUPYYZENIR-GHCJXIJMSA-N Asp-Ile-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(=O)O)N LBFYTUPYYZENIR-GHCJXIJMSA-N 0.000 description 2
- HKEZZWQWXWGASX-KKUMJFAQSA-N Asp-Leu-Phe Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 HKEZZWQWXWGASX-KKUMJFAQSA-N 0.000 description 2
- ZBYLEBZCVKLPCY-FXQIFTODSA-N Asp-Ser-Arg Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O ZBYLEBZCVKLPCY-FXQIFTODSA-N 0.000 description 2
- GWWSUMLEWKQHLR-NUMRIWBASA-N Asp-Thr-Glu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](CC(=O)O)N)O GWWSUMLEWKQHLR-NUMRIWBASA-N 0.000 description 2
- JSNWZMFSLIWAHS-HJGDQZAQSA-N Asp-Thr-Leu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CC(=O)O)N)O JSNWZMFSLIWAHS-HJGDQZAQSA-N 0.000 description 2
- ZUNMTUPRQMWMHX-LSJOCFKGSA-N Asp-Val-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(O)=O ZUNMTUPRQMWMHX-LSJOCFKGSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- BSFFNUBDVYTDMV-WHFBIAKZSA-N Cys-Gly-Asn Chemical compound [H]N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O BSFFNUBDVYTDMV-WHFBIAKZSA-N 0.000 description 2
- IXPSSIBVVKSOIE-SRVKXCTJSA-N Cys-Ser-Tyr Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CS)N)O IXPSSIBVVKSOIE-SRVKXCTJSA-N 0.000 description 2
- YWEHYKGJWHPGPY-XGEHTFHBSA-N Cys-Thr-Arg Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CS)N)O YWEHYKGJWHPGPY-XGEHTFHBSA-N 0.000 description 2
- 108010040721 Flagellin Proteins 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- RZSLYUUFFVHFRQ-FXQIFTODSA-N Gln-Ala-Glu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O RZSLYUUFFVHFRQ-FXQIFTODSA-N 0.000 description 2
- LKUWAWGNJYJODH-KBIXCLLPSA-N Gln-Ala-Ile Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O LKUWAWGNJYJODH-KBIXCLLPSA-N 0.000 description 2
- XEZWLWNGUMXAJI-QEJZJMRPSA-N Gln-Cys-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CS)NC(=O)[C@H](CCC(N)=O)N)C(O)=O)=CNC2=C1 XEZWLWNGUMXAJI-QEJZJMRPSA-N 0.000 description 2
- XKBASPWPBXNVLQ-WDSKDSINSA-N Gln-Gly-Asn Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O XKBASPWPBXNVLQ-WDSKDSINSA-N 0.000 description 2
- PBYFVIQRFLNQCO-GUBZILKMSA-N Gln-Pro-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O PBYFVIQRFLNQCO-GUBZILKMSA-N 0.000 description 2
- FQCILXROGNOZON-YUMQZZPRSA-N Gln-Pro-Gly Chemical compound NC(=O)CC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O FQCILXROGNOZON-YUMQZZPRSA-N 0.000 description 2
- XQDGOJPVMSWZSO-SRVKXCTJSA-N Gln-Pro-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)N)N XQDGOJPVMSWZSO-SRVKXCTJSA-N 0.000 description 2
- YPFFHGRJCUBXPX-NHCYSSNCSA-N Gln-Pro-Val Chemical compound CC(C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCC(N)=O)C(O)=O YPFFHGRJCUBXPX-NHCYSSNCSA-N 0.000 description 2
- WATXSTJXNBOHKD-LAEOZQHASA-N Glu-Asp-Val Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O WATXSTJXNBOHKD-LAEOZQHASA-N 0.000 description 2
- MIQCYAJSDGNCNK-BPUTZDHNSA-N Glu-Gln-Trp Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O MIQCYAJSDGNCNK-BPUTZDHNSA-N 0.000 description 2
- GXMXPCXXKVWOSM-KQXIARHKSA-N Glu-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCC(=O)O)N GXMXPCXXKVWOSM-KQXIARHKSA-N 0.000 description 2
- VMKCPNBBPGGQBJ-GUBZILKMSA-N Glu-Leu-Asn Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](CCC(=O)O)N VMKCPNBBPGGQBJ-GUBZILKMSA-N 0.000 description 2
- HQTDNEZTGZUWSY-XVKPBYJWSA-N Glu-Val-Gly Chemical compound CC(C)[C@H](NC(=O)[C@@H](N)CCC(O)=O)C(=O)NCC(O)=O HQTDNEZTGZUWSY-XVKPBYJWSA-N 0.000 description 2
- JVWPPCWUDRJGAE-YUMQZZPRSA-N Gly-Asn-Leu Chemical compound [H]NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O JVWPPCWUDRJGAE-YUMQZZPRSA-N 0.000 description 2
- XCLCVBYNGXEVDU-WHFBIAKZSA-N Gly-Asn-Ser Chemical compound NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(O)=O XCLCVBYNGXEVDU-WHFBIAKZSA-N 0.000 description 2
- LIXWIUAORXJNBH-QWRGUYRKSA-N Gly-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)CN LIXWIUAORXJNBH-QWRGUYRKSA-N 0.000 description 2
- GLACUWHUYFBSPJ-FJXKBIBVSA-N Gly-Pro-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)CN GLACUWHUYFBSPJ-FJXKBIBVSA-N 0.000 description 2
- STWGDDDFLUFCCA-GVXVVHGQSA-N His-Glu-Val Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O STWGDDDFLUFCCA-GVXVVHGQSA-N 0.000 description 2
- CZXKZMQKXQZDEX-YUMQZZPRSA-N His-Gly-Cys Chemical compound C1=C(NC=N1)C[C@@H](C(=O)NCC(=O)N[C@@H](CS)C(=O)O)N CZXKZMQKXQZDEX-YUMQZZPRSA-N 0.000 description 2
- UWSMZKRTOZEGDD-CUJWVEQBSA-N His-Thr-Ser Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O UWSMZKRTOZEGDD-CUJWVEQBSA-N 0.000 description 2
- GBMSSORHVHAYLU-QTKMDUPCSA-N His-Val-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC1=CN=CN1)N)O GBMSSORHVHAYLU-QTKMDUPCSA-N 0.000 description 2
- TZCGZYWNIDZZMR-UHFFFAOYSA-N Ile-Arg-Ala Natural products CCC(C)C(N)C(=O)NC(C(=O)NC(C)C(O)=O)CCCN=C(N)N TZCGZYWNIDZZMR-UHFFFAOYSA-N 0.000 description 2
- REXAUQBGSGDEJY-IGISWZIWSA-N Ile-Tyr-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)O)N REXAUQBGSGDEJY-IGISWZIWSA-N 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 239000005411 L01XE02 - Gefitinib Substances 0.000 description 2
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 2
- QVFGXCVIXXBFHO-AVGNSLFASA-N Leu-Glu-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O QVFGXCVIXXBFHO-AVGNSLFASA-N 0.000 description 2
- HYIFFZAQXPUEAU-QWRGUYRKSA-N Leu-Gly-Leu Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(C)C HYIFFZAQXPUEAU-QWRGUYRKSA-N 0.000 description 2
- AVEGDIAXTDVBJS-XUXIUFHCSA-N Leu-Ile-Arg Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O AVEGDIAXTDVBJS-XUXIUFHCSA-N 0.000 description 2
- QLDHBYRUNQZIJQ-DKIMLUQUSA-N Leu-Ile-Phe Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O QLDHBYRUNQZIJQ-DKIMLUQUSA-N 0.000 description 2
- LZHJZLHSRGWBBE-IHRRRGAJSA-N Leu-Lys-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O LZHJZLHSRGWBBE-IHRRRGAJSA-N 0.000 description 2
- IZPVWNSAVUQBGP-CIUDSAMLSA-N Leu-Ser-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O IZPVWNSAVUQBGP-CIUDSAMLSA-N 0.000 description 2
- FBNPMTNBFFAMMH-UHFFFAOYSA-N Leu-Val-Arg Natural products CC(C)CC(N)C(=O)NC(C(C)C)C(=O)NC(C(O)=O)CCCN=C(N)N FBNPMTNBFFAMMH-UHFFFAOYSA-N 0.000 description 2
- 108010028921 Lipopeptides Proteins 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 108090001030 Lipoproteins Proteins 0.000 description 2
- GPJGFSFYBJGYRX-YUMQZZPRSA-N Lys-Gly-Asp Chemical compound NCCCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(O)=O GPJGFSFYBJGYRX-YUMQZZPRSA-N 0.000 description 2
- OIQSIMFSVLLWBX-VOAKCMCISA-N Lys-Leu-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OIQSIMFSVLLWBX-VOAKCMCISA-N 0.000 description 2
- MCNGIXXCMJAURZ-VEVYYDQMSA-N Met-Asp-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCSC)N)O MCNGIXXCMJAURZ-VEVYYDQMSA-N 0.000 description 2
- AFVOKRHYSSFPHC-STECZYCISA-N Met-Ile-Tyr Chemical compound CSCC[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 AFVOKRHYSSFPHC-STECZYCISA-N 0.000 description 2
- ZDJICAUBMUKVEJ-CIUDSAMLSA-N Met-Ser-Gln Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(N)=O ZDJICAUBMUKVEJ-CIUDSAMLSA-N 0.000 description 2
- 241000204031 Mycoplasma Species 0.000 description 2
- SITLTJHOQZFJGG-UHFFFAOYSA-N N-L-alpha-glutamyl-L-valine Natural products CC(C)C(C(O)=O)NC(=O)C(N)CCC(O)=O SITLTJHOQZFJGG-UHFFFAOYSA-N 0.000 description 2
- XMBSYZWANAQXEV-UHFFFAOYSA-N N-alpha-L-glutamyl-L-phenylalanine Natural products OC(=O)CCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 XMBSYZWANAQXEV-UHFFFAOYSA-N 0.000 description 2
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 2
- 108010002311 N-glycylglutamic acid Proteins 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 108010067902 Peptide Library Proteins 0.000 description 2
- ZWJKVFAYPLPCQB-UNQGMJICSA-N Phe-Arg-Thr Chemical compound C[C@@H](O)[C@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)Cc1ccccc1)C(O)=O ZWJKVFAYPLPCQB-UNQGMJICSA-N 0.000 description 2
- VADLTGVIOIOKGM-BZSNNMDCSA-N Phe-His-Leu Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](N)CC=1C=CC=CC=1)C1=CN=CN1 VADLTGVIOIOKGM-BZSNNMDCSA-N 0.000 description 2
- FINLZXKJWTYYLC-ACRUOGEOSA-N Phe-His-Phe Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 FINLZXKJWTYYLC-ACRUOGEOSA-N 0.000 description 2
- YKUGPVXSDOOANW-KKUMJFAQSA-N Phe-Leu-Asp Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O YKUGPVXSDOOANW-KKUMJFAQSA-N 0.000 description 2
- ZLAKUZDMKVKFAI-JYJNAYRXSA-N Phe-Pro-Val Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O ZLAKUZDMKVKFAI-JYJNAYRXSA-N 0.000 description 2
- KLYYKKGCPOGDPE-OEAJRASXSA-N Phe-Thr-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O KLYYKKGCPOGDPE-OEAJRASXSA-N 0.000 description 2
- 108091036414 Polyinosinic:polycytidylic acid Proteins 0.000 description 2
- WPQKSRHDTMRSJM-CIUDSAMLSA-N Pro-Asp-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H]1CCCN1 WPQKSRHDTMRSJM-CIUDSAMLSA-N 0.000 description 2
- YFNOUBWUIIJQHF-LPEHRKFASA-N Pro-Asp-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC(=O)O)C(=O)N2CCC[C@@H]2C(=O)O YFNOUBWUIIJQHF-LPEHRKFASA-N 0.000 description 2
- UEHYFUCOGHWASA-HJGDQZAQSA-N Pro-Glu-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CCCN1 UEHYFUCOGHWASA-HJGDQZAQSA-N 0.000 description 2
- LPGSNRSLPHRNBW-AVGNSLFASA-N Pro-His-Val Chemical compound C([C@@H](C(=O)N[C@@H](C(C)C)C([O-])=O)NC(=O)[C@H]1[NH2+]CCC1)C1=CN=CN1 LPGSNRSLPHRNBW-AVGNSLFASA-N 0.000 description 2
- YXHYJEPDKSYPSQ-AVGNSLFASA-N Pro-Leu-Arg Chemical compound NC(N)=NCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1 YXHYJEPDKSYPSQ-AVGNSLFASA-N 0.000 description 2
- MLKVIVZCFYRTIR-KKUMJFAQSA-N Pro-Phe-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O MLKVIVZCFYRTIR-KKUMJFAQSA-N 0.000 description 2
- OWQXAJQZLWHPBH-FXQIFTODSA-N Pro-Ser-Asn Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O OWQXAJQZLWHPBH-FXQIFTODSA-N 0.000 description 2
- RNEFESSBTOQSAC-DCAQKATOSA-N Pro-Ser-His Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O RNEFESSBTOQSAC-DCAQKATOSA-N 0.000 description 2
- AIOWVDNPESPXRB-YTWAJWBKSA-N Pro-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@@H]2CCCN2)O AIOWVDNPESPXRB-YTWAJWBKSA-N 0.000 description 2
- CNUIHOAISPKQPY-HSHDSVGOSA-N Pro-Thr-Trp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O CNUIHOAISPKQPY-HSHDSVGOSA-N 0.000 description 2
- IMNVAOPEMFDAQD-NHCYSSNCSA-N Pro-Val-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O IMNVAOPEMFDAQD-NHCYSSNCSA-N 0.000 description 2
- 229940079156 Proteasome inhibitor Drugs 0.000 description 2
- NLQUOHDCLSFABG-GUBZILKMSA-N Ser-Arg-Arg Chemical compound NC(N)=NCCC[C@H](NC(=O)[C@H](CO)N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O NLQUOHDCLSFABG-GUBZILKMSA-N 0.000 description 2
- FCRMLGJMPXCAHD-FXQIFTODSA-N Ser-Arg-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(O)=O FCRMLGJMPXCAHD-FXQIFTODSA-N 0.000 description 2
- CRZRTKAVUUGKEQ-ACZMJKKPSA-N Ser-Gln-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(O)=O CRZRTKAVUUGKEQ-ACZMJKKPSA-N 0.000 description 2
- UOLGINIHBRIECN-FXQIFTODSA-N Ser-Glu-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O UOLGINIHBRIECN-FXQIFTODSA-N 0.000 description 2
- XGQKSRGHEZNWIS-IHRRRGAJSA-N Ser-Pro-Tyr Chemical compound N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccc(O)cc1)C(O)=O XGQKSRGHEZNWIS-IHRRRGAJSA-N 0.000 description 2
- FZXOPYUEQGDGMS-ACZMJKKPSA-N Ser-Ser-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O FZXOPYUEQGDGMS-ACZMJKKPSA-N 0.000 description 2
- VAIWUNAAPZZGRI-IHPCNDPISA-N Ser-Trp-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)NC(=O)[C@H](CO)N VAIWUNAAPZZGRI-IHPCNDPISA-N 0.000 description 2
- FGBLCMLXHRPVOF-IHRRRGAJSA-N Ser-Tyr-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O FGBLCMLXHRPVOF-IHRRRGAJSA-N 0.000 description 2
- SIEBDTCABMZCLF-XGEHTFHBSA-N Ser-Val-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O SIEBDTCABMZCLF-XGEHTFHBSA-N 0.000 description 2
- 241000589970 Spirochaetales Species 0.000 description 2
- NAVMQTYZDKMPEU-UHFFFAOYSA-N Targretin Chemical compound CC1=CC(C(CCC2(C)C)(C)C)=C2C=C1C(=C)C1=CC=C(C(O)=O)C=C1 NAVMQTYZDKMPEU-UHFFFAOYSA-N 0.000 description 2
- YOSLMIPKOUAHKI-OLHMAJIHSA-N Thr-Asp-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O YOSLMIPKOUAHKI-OLHMAJIHSA-N 0.000 description 2
- UCCNDUPVIFOOQX-CUJWVEQBSA-N Thr-Cys-His Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 UCCNDUPVIFOOQX-CUJWVEQBSA-N 0.000 description 2
- VRUFCJZQDACGLH-UVOCVTCTSA-N Thr-Leu-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VRUFCJZQDACGLH-UVOCVTCTSA-N 0.000 description 2
- GYUUYCIXELGTJS-MEYUZBJRSA-N Thr-Phe-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)N)O GYUUYCIXELGTJS-MEYUZBJRSA-N 0.000 description 2
- WNQJTLATMXYSEL-OEAJRASXSA-N Thr-Phe-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(O)=O WNQJTLATMXYSEL-OEAJRASXSA-N 0.000 description 2
- SPIFGZFZMVLPHN-UNQGMJICSA-N Thr-Val-Phe Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O SPIFGZFZMVLPHN-UNQGMJICSA-N 0.000 description 2
- 102000002689 Toll-like receptor Human genes 0.000 description 2
- 108020000411 Toll-like receptor Proteins 0.000 description 2
- CCZXBOFIBYQLEV-IHPCNDPISA-N Trp-Leu-Leu Chemical compound CC(C)C[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)Cc1c[nH]c2ccccc12)C(O)=O CCZXBOFIBYQLEV-IHPCNDPISA-N 0.000 description 2
- VCGOTJGGBXEBFO-FDARSICLSA-N Trp-Pro-Ile Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(O)=O VCGOTJGGBXEBFO-FDARSICLSA-N 0.000 description 2
- IVXJODPZRWHCCR-JYJNAYRXSA-N Val-Arg-Phe Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)N IVXJODPZRWHCCR-JYJNAYRXSA-N 0.000 description 2
- DNOOLPROHJWCSQ-RCWTZXSCSA-N Val-Arg-Thr Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O DNOOLPROHJWCSQ-RCWTZXSCSA-N 0.000 description 2
- LAYSXAOGWHKNED-XPUUQOCRSA-N Val-Gly-Ser Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O LAYSXAOGWHKNED-XPUUQOCRSA-N 0.000 description 2
- YDVDTCJGBBJGRT-GUBZILKMSA-N Val-Met-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)O)N YDVDTCJGBBJGRT-GUBZILKMSA-N 0.000 description 2
- NHXZRXLFOBFMDM-AVGNSLFASA-N Val-Pro-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)C(C)C NHXZRXLFOBFMDM-AVGNSLFASA-N 0.000 description 2
- VHIZXDZMTDVFGX-DCAQKATOSA-N Val-Ser-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)N VHIZXDZMTDVFGX-DCAQKATOSA-N 0.000 description 2
- QTPQHINADBYBNA-DCAQKATOSA-N Val-Ser-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCCN QTPQHINADBYBNA-DCAQKATOSA-N 0.000 description 2
- DLLRRUDLMSJTMB-GUBZILKMSA-N Val-Ser-Met Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)O)N DLLRRUDLMSJTMB-GUBZILKMSA-N 0.000 description 2
- OFTXTCGQJXTNQS-XGEHTFHBSA-N Val-Thr-Ser Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](C(C)C)N)O OFTXTCGQJXTNQS-XGEHTFHBSA-N 0.000 description 2
- PFMSJVIPEZMKSC-DZKIICNBSA-N Val-Tyr-Glu Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N PFMSJVIPEZMKSC-DZKIICNBSA-N 0.000 description 2
- IECQJCJNPJVUSB-IHRRRGAJSA-N Val-Tyr-Ser Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CO)C(O)=O IECQJCJNPJVUSB-IHRRRGAJSA-N 0.000 description 2
- RTJPAGFXOWEBAI-SRVKXCTJSA-N Val-Val-Arg Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N RTJPAGFXOWEBAI-SRVKXCTJSA-N 0.000 description 2
- 239000002250 absorbent Substances 0.000 description 2
- 230000002745 absorbent Effects 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 108010041407 alanylaspartic acid Proteins 0.000 description 2
- 108010087924 alanylproline Proteins 0.000 description 2
- NWMHDZMRVUOQGL-CZEIJOLGSA-N almurtide Chemical compound OC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)CO[C@@H]([C@H](O)[C@H](O)CO)[C@@H](NC(C)=O)C=O NWMHDZMRVUOQGL-CZEIJOLGSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000000611 antibody drug conjugate Substances 0.000 description 2
- 229940049595 antibody-drug conjugate Drugs 0.000 description 2
- 108010008355 arginyl-glutamine Proteins 0.000 description 2
- 108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 description 2
- 108010068380 arginylarginine Proteins 0.000 description 2
- 108010040443 aspartyl-aspartic acid Proteins 0.000 description 2
- 108010069205 aspartyl-phenylalanine Proteins 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 229960000397 bevacizumab Drugs 0.000 description 2
- 229960002938 bexarotene Drugs 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 210000004899 c-terminal region Anatomy 0.000 description 2
- 150000001720 carbohydrates Chemical group 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 229960005395 cetuximab Drugs 0.000 description 2
- SQQXRXKYTKFFSM-UHFFFAOYSA-N chembl1992147 Chemical compound OC1=C(OC)C(OC)=CC=C1C1=C(C)C(C(O)=O)=NC(C=2N=C3C4=NC(C)(C)N=C4C(OC)=C(O)C3=CC=2)=C1N SQQXRXKYTKFFSM-UHFFFAOYSA-N 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 2
- 108010016616 cysteinylglycine Proteins 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 231100000517 death Toxicity 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229960003668 docetaxel Drugs 0.000 description 2
- 229940121647 egfr inhibitor Drugs 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 229960001433 erlotinib Drugs 0.000 description 2
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 239000011888 foil Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000003517 fume Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 229960002584 gefitinib Drugs 0.000 description 2
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 2
- 108010082286 glycyl-seryl-alanine Proteins 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 108010018006 histidylserine Proteins 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 229940124669 imidazoquinoline Drugs 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000002998 immunogenetic effect Effects 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 230000002055 immunohistochemical effect Effects 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 230000002637 immunotoxin Effects 0.000 description 2
- 239000002596 immunotoxin Substances 0.000 description 2
- 229940051026 immunotoxin Drugs 0.000 description 2
- 231100000608 immunotoxin Toxicity 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000001361 intraarterial administration Methods 0.000 description 2
- 108010034529 leucyl-lysine Proteins 0.000 description 2
- 229920006008 lipopolysaccharide Polymers 0.000 description 2
- 201000005249 lung adenocarcinoma Diseases 0.000 description 2
- 108010003700 lysyl aspartic acid Proteins 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 108010012581 phenylalanylglutamate Proteins 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 108010007513 prolyl-glycyl-prolyl-leucine Proteins 0.000 description 2
- 108010031719 prolyl-serine Proteins 0.000 description 2
- 108010029020 prolylglycine Proteins 0.000 description 2
- 239000003207 proteasome inhibitor Substances 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 108010069117 seryl-lysyl-aspartic acid Proteins 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 108010080629 tryptophan-leucine Proteins 0.000 description 2
- 108010038745 tryptophylglycine Proteins 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- 108010073969 valyllysine Proteins 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- CEHZCZCQHUNAJF-AVGNSLFASA-N (2s)-1-[2-[[(2s)-1-[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]acetyl]pyrrolidine-2-carboxylic acid Chemical compound NC(N)=NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N1[C@H](C(O)=O)CCC1 CEHZCZCQHUNAJF-AVGNSLFASA-N 0.000 description 1
- AEGSIYIIMVBZQU-CIUDSAMLSA-N (3s)-3-[[2-[[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]acetyl]amino]-4-[[(1r)-1-carboxy-2-sulfanylethyl]amino]-4-oxobutanoic acid Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CS)C(O)=O AEGSIYIIMVBZQU-CIUDSAMLSA-N 0.000 description 1
- YHQZWWDVLJPRIF-JLHRHDQISA-N (4R)-4-[[(2S,3R)-2-[acetyl-[(3R,4R,5S,6R)-3-amino-4-[(1R)-1-carboxyethoxy]-5-hydroxy-6-(hydroxymethyl)oxan-2-yl]amino]-3-hydroxybutanoyl]amino]-5-amino-5-oxopentanoic acid Chemical compound C(C)(=O)N([C@@H]([C@H](O)C)C(=O)N[C@H](CCC(=O)O)C(N)=O)C1[C@H](N)[C@@H](O[C@@H](C(=O)O)C)[C@H](O)[C@H](O1)CO YHQZWWDVLJPRIF-JLHRHDQISA-N 0.000 description 1
- 108091064702 1 family Proteins 0.000 description 1
- VQFKFAKEUMHBLV-BYSUZVQFSA-N 1-O-(alpha-D-galactosyl)-N-hexacosanoylphytosphingosine Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCC(=O)N[C@H]([C@H](O)[C@H](O)CCCCCCCCCCCCCC)CO[C@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQFKFAKEUMHBLV-BYSUZVQFSA-N 0.000 description 1
- PNDPGZBMCMUPRI-HVTJNCQCSA-N 10043-66-0 Chemical compound [131I][131I] PNDPGZBMCMUPRI-HVTJNCQCSA-N 0.000 description 1
- 101150082952 ACTA1 gene Proteins 0.000 description 1
- WQVFQXXBNHHPLX-ZKWXMUAHSA-N Ala-Ala-His Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O WQVFQXXBNHHPLX-ZKWXMUAHSA-N 0.000 description 1
- UCIYCBSJBQGDGM-LPEHRKFASA-N Ala-Arg-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@@H]1C(=O)O)N UCIYCBSJBQGDGM-LPEHRKFASA-N 0.000 description 1
- GFBLJMHGHAXGNY-ZLUOBGJFSA-N Ala-Asn-Asp Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O GFBLJMHGHAXGNY-ZLUOBGJFSA-N 0.000 description 1
- IKKVASZHTMKJIR-ZKWXMUAHSA-N Ala-Asp-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O IKKVASZHTMKJIR-ZKWXMUAHSA-N 0.000 description 1
- FRFDXQWNDZMREB-ACZMJKKPSA-N Ala-Cys-Gln Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(O)=O FRFDXQWNDZMREB-ACZMJKKPSA-N 0.000 description 1
- OILNWMNBLIHXQK-ZLUOBGJFSA-N Ala-Cys-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(O)=O OILNWMNBLIHXQK-ZLUOBGJFSA-N 0.000 description 1
- CZPAHAKGPDUIPJ-CIUDSAMLSA-N Ala-Gln-Pro Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(O)=O CZPAHAKGPDUIPJ-CIUDSAMLSA-N 0.000 description 1
- BGNLUHXLSAQYRQ-FXQIFTODSA-N Ala-Glu-Gln Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O BGNLUHXLSAQYRQ-FXQIFTODSA-N 0.000 description 1
- GGNHBHYDMUDXQB-KBIXCLLPSA-N Ala-Glu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)N GGNHBHYDMUDXQB-KBIXCLLPSA-N 0.000 description 1
- MPLOSMWGDNJSEV-WHFBIAKZSA-N Ala-Gly-Asp Chemical compound [H]N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O MPLOSMWGDNJSEV-WHFBIAKZSA-N 0.000 description 1
- DCUCOIYYUBILPS-GUBZILKMSA-N Ala-Leu-Asp-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O DCUCOIYYUBILPS-GUBZILKMSA-N 0.000 description 1
- OYJCVIGKMXUVKB-GARJFASQSA-N Ala-Leu-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N OYJCVIGKMXUVKB-GARJFASQSA-N 0.000 description 1
- MEFILNJXAVSUTO-JXUBOQSCSA-N Ala-Leu-Thr Chemical compound C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O MEFILNJXAVSUTO-JXUBOQSCSA-N 0.000 description 1
- GKAZXNDATBWNBI-DCAQKATOSA-N Ala-Met-Lys Chemical compound C[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)O)N GKAZXNDATBWNBI-DCAQKATOSA-N 0.000 description 1
- 108010011667 Ala-Phe-Ala Proteins 0.000 description 1
- XWFWAXPOLRTDFZ-FXQIFTODSA-N Ala-Pro-Ser Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O XWFWAXPOLRTDFZ-FXQIFTODSA-N 0.000 description 1
- VJVQKGYHIZPSNS-FXQIFTODSA-N Ala-Ser-Arg Chemical compound C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCN=C(N)N VJVQKGYHIZPSNS-FXQIFTODSA-N 0.000 description 1
- RTZCUEHYUQZIDE-WHFBIAKZSA-N Ala-Ser-Gly Chemical compound C[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O RTZCUEHYUQZIDE-WHFBIAKZSA-N 0.000 description 1
- DYXOFPBJBAHWFY-JBDRJPRFSA-N Ala-Ser-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](C)N DYXOFPBJBAHWFY-JBDRJPRFSA-N 0.000 description 1
- HOVPGJUNRLMIOZ-CIUDSAMLSA-N Ala-Ser-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](C)N HOVPGJUNRLMIOZ-CIUDSAMLSA-N 0.000 description 1
- WQKAQKZRDIZYNV-VZFHVOOUSA-N Ala-Ser-Thr Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O WQKAQKZRDIZYNV-VZFHVOOUSA-N 0.000 description 1
- ARHJJAAWNWOACN-FXQIFTODSA-N Ala-Ser-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O ARHJJAAWNWOACN-FXQIFTODSA-N 0.000 description 1
- XQNRANMFRPCFFW-GCJQMDKQSA-N Ala-Thr-Asn Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](C)N)O XQNRANMFRPCFFW-GCJQMDKQSA-N 0.000 description 1
- HCBKAOZYACJUEF-XQXXSGGOSA-N Ala-Thr-Gln Chemical compound N[C@@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CCC(N)=O)C(=O)O HCBKAOZYACJUEF-XQXXSGGOSA-N 0.000 description 1
- SAHQGRZIQVEJPF-JXUBOQSCSA-N Ala-Thr-Lys Chemical compound C[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CCCCN SAHQGRZIQVEJPF-JXUBOQSCSA-N 0.000 description 1
- QOIGKCBMXUCDQU-KDXUFGMBSA-N Ala-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](C)N)O QOIGKCBMXUCDQU-KDXUFGMBSA-N 0.000 description 1
- KTXKIYXZQFWJKB-VZFHVOOUSA-N Ala-Thr-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O KTXKIYXZQFWJKB-VZFHVOOUSA-N 0.000 description 1
- IETUUAHKCHOQHP-KZVJFYERSA-N Ala-Thr-Val Chemical compound CC(C)[C@H](NC(=O)[C@@H](NC(=O)[C@H](C)N)[C@@H](C)O)C(O)=O IETUUAHKCHOQHP-KZVJFYERSA-N 0.000 description 1
- AENHOIXXHKNIQL-AUTRQRHGSA-N Ala-Tyr-Ala Chemical compound [O-]C(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H]([NH3+])C)CC1=CC=C(O)C=C1 AENHOIXXHKNIQL-AUTRQRHGSA-N 0.000 description 1
- XSLGWYYNOSUMRM-ZKWXMUAHSA-N Ala-Val-Asn Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O XSLGWYYNOSUMRM-ZKWXMUAHSA-N 0.000 description 1
- LYILPUNCKACNGF-NAKRPEOUSA-N Ala-Val-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C)N LYILPUNCKACNGF-NAKRPEOUSA-N 0.000 description 1
- VBFJESQBIWCWRL-DCAQKATOSA-N Arg-Ala-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCNC(N)=N VBFJESQBIWCWRL-DCAQKATOSA-N 0.000 description 1
- VWVPYNGMOCSSGK-GUBZILKMSA-N Arg-Arg-Asn Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(O)=O VWVPYNGMOCSSGK-GUBZILKMSA-N 0.000 description 1
- KJGNDQCYBNBXDA-GUBZILKMSA-N Arg-Arg-Cys Chemical compound C(C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CS)C(=O)O)N)CN=C(N)N KJGNDQCYBNBXDA-GUBZILKMSA-N 0.000 description 1
- MUXONAMCEUBVGA-DCAQKATOSA-N Arg-Arg-Gln Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(N)=O)C(O)=O MUXONAMCEUBVGA-DCAQKATOSA-N 0.000 description 1
- UISQLSIBJKEJSS-GUBZILKMSA-N Arg-Arg-Ser Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CO)C(O)=O UISQLSIBJKEJSS-GUBZILKMSA-N 0.000 description 1
- NABSCJGZKWSNHX-RCWTZXSCSA-N Arg-Arg-Thr Chemical compound NC(N)=NCCC[C@@H](C(=O)N[C@@H]([C@H](O)C)C(O)=O)NC(=O)[C@@H](N)CCCN=C(N)N NABSCJGZKWSNHX-RCWTZXSCSA-N 0.000 description 1
- DPNHSNLIULPOBH-GUBZILKMSA-N Arg-Asn-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCN=C(N)N)N DPNHSNLIULPOBH-GUBZILKMSA-N 0.000 description 1
- XVLLUZMFSAYKJV-GUBZILKMSA-N Arg-Asp-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O XVLLUZMFSAYKJV-GUBZILKMSA-N 0.000 description 1
- NTAZNGWBXRVEDJ-FXQIFTODSA-N Arg-Asp-Asp Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O NTAZNGWBXRVEDJ-FXQIFTODSA-N 0.000 description 1
- KMSHNDWHPWXPEC-BQBZGAKWSA-N Arg-Asp-Gly Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O KMSHNDWHPWXPEC-BQBZGAKWSA-N 0.000 description 1
- MFAMTAVAFBPXDC-LPEHRKFASA-N Arg-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O MFAMTAVAFBPXDC-LPEHRKFASA-N 0.000 description 1
- HKRXJBBCQBAGIM-FXQIFTODSA-N Arg-Asp-Ser Chemical compound C(C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)O)N)CN=C(N)N HKRXJBBCQBAGIM-FXQIFTODSA-N 0.000 description 1
- VXXHDZKEQNGXNU-QXEWZRGKSA-N Arg-Asp-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CCCN=C(N)N VXXHDZKEQNGXNU-QXEWZRGKSA-N 0.000 description 1
- RWDVGVPHEWOZMO-GUBZILKMSA-N Arg-Cys-Val Chemical compound CC(C)[C@H](NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCCNC(N)=N)C(O)=O RWDVGVPHEWOZMO-GUBZILKMSA-N 0.000 description 1
- GIVWETPOBCRTND-DCAQKATOSA-N Arg-Gln-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O GIVWETPOBCRTND-DCAQKATOSA-N 0.000 description 1
- ZEAYJGRKRUBDOB-GARJFASQSA-N Arg-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O ZEAYJGRKRUBDOB-GARJFASQSA-N 0.000 description 1
- OHYQKYUTLIPFOX-ZPFDUUQYSA-N Arg-Glu-Ile Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O OHYQKYUTLIPFOX-ZPFDUUQYSA-N 0.000 description 1
- HPSVTWMFWCHKFN-GARJFASQSA-N Arg-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O HPSVTWMFWCHKFN-GARJFASQSA-N 0.000 description 1
- GOWZVQXTHUCNSQ-NHCYSSNCSA-N Arg-Glu-Val Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O GOWZVQXTHUCNSQ-NHCYSSNCSA-N 0.000 description 1
- AQPVUEJJARLJHB-BQBZGAKWSA-N Arg-Gly-Ala Chemical compound OC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](N)CCCN=C(N)N AQPVUEJJARLJHB-BQBZGAKWSA-N 0.000 description 1
- UBCPNBUIQNMDNH-NAKRPEOUSA-N Arg-Ile-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O UBCPNBUIQNMDNH-NAKRPEOUSA-N 0.000 description 1
- CLICCYPMVFGUOF-IHRRRGAJSA-N Arg-Lys-Leu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O CLICCYPMVFGUOF-IHRRRGAJSA-N 0.000 description 1
- JBIRFLWXWDSDTR-CYDGBPFRSA-N Arg-Met-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCN=C(N)N)N JBIRFLWXWDSDTR-CYDGBPFRSA-N 0.000 description 1
- KSUALAGYYLQSHJ-RCWTZXSCSA-N Arg-Met-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KSUALAGYYLQSHJ-RCWTZXSCSA-N 0.000 description 1
- FKQITMVNILRUCQ-IHRRRGAJSA-N Arg-Phe-Asp Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O FKQITMVNILRUCQ-IHRRRGAJSA-N 0.000 description 1
- FIQKRDXFTANIEJ-ULQDDVLXSA-N Arg-Phe-His Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N FIQKRDXFTANIEJ-ULQDDVLXSA-N 0.000 description 1
- IGFJVXOATGZTHD-UHFFFAOYSA-N Arg-Phe-His Natural products NC(CCNC(=N)N)C(=O)NC(Cc1ccccc1)C(=O)NC(Cc2c[nH]cn2)C(=O)O IGFJVXOATGZTHD-UHFFFAOYSA-N 0.000 description 1
- DNBMCNQKNOKOSD-DCAQKATOSA-N Arg-Pro-Gln Chemical compound NC(N)=NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O DNBMCNQKNOKOSD-DCAQKATOSA-N 0.000 description 1
- XSPKAHFVDKRGRL-DCAQKATOSA-N Arg-Pro-Glu Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O XSPKAHFVDKRGRL-DCAQKATOSA-N 0.000 description 1
- 108010051330 Arg-Pro-Gly-Pro Proteins 0.000 description 1
- IJYZHIOOBGIINM-WDSKDSINSA-N Arg-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H](N)CCCN=C(N)N IJYZHIOOBGIINM-WDSKDSINSA-N 0.000 description 1
- KXOPYFNQLVUOAQ-FXQIFTODSA-N Arg-Ser-Ala Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O KXOPYFNQLVUOAQ-FXQIFTODSA-N 0.000 description 1
- ASQKVGRCKOFKIU-KZVJFYERSA-N Arg-Thr-Ala Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](C)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)O ASQKVGRCKOFKIU-KZVJFYERSA-N 0.000 description 1
- WCZXPVPHUMYLMS-VEVYYDQMSA-N Arg-Thr-Asp Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O WCZXPVPHUMYLMS-VEVYYDQMSA-N 0.000 description 1
- ZPWMEWYQBWSGAO-ZJDVBMNYSA-N Arg-Thr-Thr Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O ZPWMEWYQBWSGAO-ZJDVBMNYSA-N 0.000 description 1
- XRNXPIGJPQHCPC-RCWTZXSCSA-N Arg-Thr-Val Chemical compound CC(C)[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CCCNC(N)=N)[C@@H](C)O)C(O)=O XRNXPIGJPQHCPC-RCWTZXSCSA-N 0.000 description 1
- VYZBPPBKFCHCIS-WPRPVWTQSA-N Arg-Val-Gly Chemical compound OC(=O)CNC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CCCN=C(N)N VYZBPPBKFCHCIS-WPRPVWTQSA-N 0.000 description 1
- XEOXPCNONWHHSW-AVGNSLFASA-N Arg-Val-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N XEOXPCNONWHHSW-AVGNSLFASA-N 0.000 description 1
- FXGMURPOWCKNAZ-JYJNAYRXSA-N Arg-Val-Phe Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 FXGMURPOWCKNAZ-JYJNAYRXSA-N 0.000 description 1
- LEFKSBYHUGUWLP-ACZMJKKPSA-N Asn-Ala-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O LEFKSBYHUGUWLP-ACZMJKKPSA-N 0.000 description 1
- HZPSDHRYYIORKR-WHFBIAKZSA-N Asn-Ala-Gly Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H](N)CC(N)=O HZPSDHRYYIORKR-WHFBIAKZSA-N 0.000 description 1
- IARGXWMWRFOQPG-GCJQMDKQSA-N Asn-Ala-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IARGXWMWRFOQPG-GCJQMDKQSA-N 0.000 description 1
- GMRGSBAMMMVDGG-GUBZILKMSA-N Asn-Arg-Arg Chemical compound C(C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CC(=O)N)N)CN=C(N)N GMRGSBAMMMVDGG-GUBZILKMSA-N 0.000 description 1
- MFFOYNGMOYFPBD-DCAQKATOSA-N Asn-Arg-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O MFFOYNGMOYFPBD-DCAQKATOSA-N 0.000 description 1
- VYLVOMUVLMGCRF-ZLUOBGJFSA-N Asn-Asp-Ser Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O VYLVOMUVLMGCRF-ZLUOBGJFSA-N 0.000 description 1
- XQQVCUIBGYFKDC-OLHMAJIHSA-N Asn-Asp-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XQQVCUIBGYFKDC-OLHMAJIHSA-N 0.000 description 1
- QRHYAUYXBVVDSB-LKXGYXEUSA-N Asn-Cys-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QRHYAUYXBVVDSB-LKXGYXEUSA-N 0.000 description 1
- MSBDSTRUMZFSEU-PEFMBERDSA-N Asn-Glu-Ile Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O MSBDSTRUMZFSEU-PEFMBERDSA-N 0.000 description 1
- JREOBWLIZLXRIS-GUBZILKMSA-N Asn-Glu-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O JREOBWLIZLXRIS-GUBZILKMSA-N 0.000 description 1
- DDPXDCKYWDGZAL-BQBZGAKWSA-N Asn-Gly-Arg Chemical compound NC(=O)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCCN=C(N)N DDPXDCKYWDGZAL-BQBZGAKWSA-N 0.000 description 1
- NCFJQJRLQJEECD-NHCYSSNCSA-N Asn-Leu-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O NCFJQJRLQJEECD-NHCYSSNCSA-N 0.000 description 1
- NYGILGUOUOXGMJ-YUMQZZPRSA-N Asn-Lys-Gly Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O NYGILGUOUOXGMJ-YUMQZZPRSA-N 0.000 description 1
- IDUUACUJKUXKKD-VEVYYDQMSA-N Asn-Pro-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O IDUUACUJKUXKKD-VEVYYDQMSA-N 0.000 description 1
- XTMZYFMTYJNABC-ZLUOBGJFSA-N Asn-Ser-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)N)N XTMZYFMTYJNABC-ZLUOBGJFSA-N 0.000 description 1
- KYQJHBWHRASMKG-ZLUOBGJFSA-N Asn-Ser-Cys Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(O)=O KYQJHBWHRASMKG-ZLUOBGJFSA-N 0.000 description 1
- DOURAOODTFJRIC-CIUDSAMLSA-N Asn-Ser-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)N)N DOURAOODTFJRIC-CIUDSAMLSA-N 0.000 description 1
- MKJBPDLENBUHQU-CIUDSAMLSA-N Asn-Ser-Leu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O MKJBPDLENBUHQU-CIUDSAMLSA-N 0.000 description 1
- MYTHOBCLNIOFBL-SRVKXCTJSA-N Asn-Ser-Tyr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O MYTHOBCLNIOFBL-SRVKXCTJSA-N 0.000 description 1
- UXHYOWXTJLBEPG-GSSVUCPTSA-N Asn-Thr-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O UXHYOWXTJLBEPG-GSSVUCPTSA-N 0.000 description 1
- BCADFFUQHIMQAA-KKHAAJSZSA-N Asn-Thr-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O BCADFFUQHIMQAA-KKHAAJSZSA-N 0.000 description 1
- QTKYFZCMSQLYHI-UBHSHLNASA-N Asn-Trp-Asn Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(N)=O)C(O)=O QTKYFZCMSQLYHI-UBHSHLNASA-N 0.000 description 1
- MYRLSKYSMXNLLA-LAEOZQHASA-N Asn-Val-Glu Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O MYRLSKYSMXNLLA-LAEOZQHASA-N 0.000 description 1
- XOQYDFCQPWAMSA-KKHAAJSZSA-N Asn-Val-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XOQYDFCQPWAMSA-KKHAAJSZSA-N 0.000 description 1
- KRXIWXCXOARFNT-ZLUOBGJFSA-N Asp-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O KRXIWXCXOARFNT-ZLUOBGJFSA-N 0.000 description 1
- PBVLJOIPOGUQQP-CIUDSAMLSA-N Asp-Ala-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O PBVLJOIPOGUQQP-CIUDSAMLSA-N 0.000 description 1
- XPGVTUBABLRGHY-BIIVOSGPSA-N Asp-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)O)N XPGVTUBABLRGHY-BIIVOSGPSA-N 0.000 description 1
- GVPSCJQLUGIKAM-GUBZILKMSA-N Asp-Arg-Arg Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O GVPSCJQLUGIKAM-GUBZILKMSA-N 0.000 description 1
- GWTLRDMPMJCNMH-WHFBIAKZSA-N Asp-Asn-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O GWTLRDMPMJCNMH-WHFBIAKZSA-N 0.000 description 1
- VBVKSAFJPVXMFJ-CIUDSAMLSA-N Asp-Asn-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(=O)O)N VBVKSAFJPVXMFJ-CIUDSAMLSA-N 0.000 description 1
- XACXDSRQIXRMNS-OLHMAJIHSA-N Asp-Asn-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CC(=O)O)N)O XACXDSRQIXRMNS-OLHMAJIHSA-N 0.000 description 1
- QXHVOUSPVAWEMX-ZLUOBGJFSA-N Asp-Asp-Ser Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O QXHVOUSPVAWEMX-ZLUOBGJFSA-N 0.000 description 1
- QQXOYLWJQUPXJU-WHFBIAKZSA-N Asp-Cys-Gly Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CS)C(=O)NCC(O)=O QQXOYLWJQUPXJU-WHFBIAKZSA-N 0.000 description 1
- DTNUIAJCPRMNBT-WHFBIAKZSA-N Asp-Gly-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](C)C(O)=O DTNUIAJCPRMNBT-WHFBIAKZSA-N 0.000 description 1
- KHGPWGKPYHPOIK-QWRGUYRKSA-N Asp-Gly-Phe Chemical compound [H]N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O KHGPWGKPYHPOIK-QWRGUYRKSA-N 0.000 description 1
- PAYPSKIBMDHZPI-CIUDSAMLSA-N Asp-Leu-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(O)=O PAYPSKIBMDHZPI-CIUDSAMLSA-N 0.000 description 1
- DWOGMPWRQQWPPF-GUBZILKMSA-N Asp-Leu-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O DWOGMPWRQQWPPF-GUBZILKMSA-N 0.000 description 1
- CJUKAWUWBZCTDQ-SRVKXCTJSA-N Asp-Leu-Lys Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O CJUKAWUWBZCTDQ-SRVKXCTJSA-N 0.000 description 1
- IVPNEDNYYYFAGI-GARJFASQSA-N Asp-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)O)N IVPNEDNYYYFAGI-GARJFASQSA-N 0.000 description 1
- UMHUHHJMEXNSIV-CIUDSAMLSA-N Asp-Leu-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(O)=O UMHUHHJMEXNSIV-CIUDSAMLSA-N 0.000 description 1
- XWSIYTYNLKCLJB-CIUDSAMLSA-N Asp-Lys-Asn Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(O)=O XWSIYTYNLKCLJB-CIUDSAMLSA-N 0.000 description 1
- MYLZFUMPZCPJCJ-NHCYSSNCSA-N Asp-Lys-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O MYLZFUMPZCPJCJ-NHCYSSNCSA-N 0.000 description 1
- HXVILZUZXFLVEN-DCAQKATOSA-N Asp-Met-Leu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(O)=O HXVILZUZXFLVEN-DCAQKATOSA-N 0.000 description 1
- RRUWMFBLFLUZSI-LPEHRKFASA-N Asp-Met-Pro Chemical compound CSCC[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC(=O)O)N RRUWMFBLFLUZSI-LPEHRKFASA-N 0.000 description 1
- KESWRFKUZRUTAH-FXQIFTODSA-N Asp-Pro-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O KESWRFKUZRUTAH-FXQIFTODSA-N 0.000 description 1
- AHWRSSLYSGLBGD-CIUDSAMLSA-N Asp-Pro-Glu Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O AHWRSSLYSGLBGD-CIUDSAMLSA-N 0.000 description 1
- QTIZKMMLNUMHHU-DCAQKATOSA-N Asp-Pro-His Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CC(=O)O)N)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O QTIZKMMLNUMHHU-DCAQKATOSA-N 0.000 description 1
- BKOIIURTQAJHAT-GUBZILKMSA-N Asp-Pro-Pro Chemical compound OC(=O)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 BKOIIURTQAJHAT-GUBZILKMSA-N 0.000 description 1
- XXAMCEGRCZQGEM-ZLUOBGJFSA-N Asp-Ser-Asn Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O XXAMCEGRCZQGEM-ZLUOBGJFSA-N 0.000 description 1
- ZVGRHIRJLWBWGJ-ACZMJKKPSA-N Asp-Ser-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O ZVGRHIRJLWBWGJ-ACZMJKKPSA-N 0.000 description 1
- NBKLEMWHDLAUEM-CIUDSAMLSA-N Asp-Ser-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)N NBKLEMWHDLAUEM-CIUDSAMLSA-N 0.000 description 1
- DRCOAZZDQRCGGP-GHCJXIJMSA-N Asp-Ser-Ile Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O DRCOAZZDQRCGGP-GHCJXIJMSA-N 0.000 description 1
- ZQFRDAZBTSFGGW-SRVKXCTJSA-N Asp-Ser-Phe Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O ZQFRDAZBTSFGGW-SRVKXCTJSA-N 0.000 description 1
- MGSVBZIBCCKGCY-ZLUOBGJFSA-N Asp-Ser-Ser Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O MGSVBZIBCCKGCY-ZLUOBGJFSA-N 0.000 description 1
- XYPJXLLXNSAWHZ-SRVKXCTJSA-N Asp-Ser-Tyr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O XYPJXLLXNSAWHZ-SRVKXCTJSA-N 0.000 description 1
- IWLZBRTUIVXZJD-OLHMAJIHSA-N Asp-Thr-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O IWLZBRTUIVXZJD-OLHMAJIHSA-N 0.000 description 1
- HCOQNGIHSXICCB-IHRRRGAJSA-N Asp-Tyr-Arg Chemical compound N[C@@H](CC(=O)O)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)O HCOQNGIHSXICCB-IHRRRGAJSA-N 0.000 description 1
- OTKUAVXGMREHRX-CFMVVWHZSA-N Asp-Tyr-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(O)=O)CC1=CC=C(O)C=C1 OTKUAVXGMREHRX-CFMVVWHZSA-N 0.000 description 1
- QOJJMJKTMKNFEF-ZKWXMUAHSA-N Asp-Val-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC(O)=O QOJJMJKTMKNFEF-ZKWXMUAHSA-N 0.000 description 1
- RKXVTTIQNKPCHU-KKHAAJSZSA-N Asp-Val-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC(O)=O RKXVTTIQNKPCHU-KKHAAJSZSA-N 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 102000008096 B7-H1 Antigen Human genes 0.000 description 1
- 108010074708 B7-H1 Antigen Proteins 0.000 description 1
- 206010060999 Benign neoplasm Diseases 0.000 description 1
- 101800001415 Bri23 peptide Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 101800000655 C-terminal peptide Proteins 0.000 description 1
- 102400000107 C-terminal peptide Human genes 0.000 description 1
- 101150013553 CD40 gene Proteins 0.000 description 1
- 101100507655 Canis lupus familiaris HSPA1 gene Proteins 0.000 description 1
- 229940093444 Cyclooxygenase 2 inhibitor Drugs 0.000 description 1
- KKZHXOOZHFABQQ-UWJYBYFXSA-N Cys-Ala-Tyr Chemical compound SC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 KKZHXOOZHFABQQ-UWJYBYFXSA-N 0.000 description 1
- GSNRZJNHMVMOFV-ACZMJKKPSA-N Cys-Asp-Glu Chemical compound C(CC(=O)O)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CS)N GSNRZJNHMVMOFV-ACZMJKKPSA-N 0.000 description 1
- DVKQPQKQDHHFTE-ZLUOBGJFSA-N Cys-Cys-Asn Chemical compound C([C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CS)N)C(=O)N DVKQPQKQDHHFTE-ZLUOBGJFSA-N 0.000 description 1
- GHUVBPIYQYXXEF-SRVKXCTJSA-N Cys-Cys-Tyr Chemical compound SC[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 GHUVBPIYQYXXEF-SRVKXCTJSA-N 0.000 description 1
- WVLZTXGTNGHPBO-SRVKXCTJSA-N Cys-Leu-Leu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O WVLZTXGTNGHPBO-SRVKXCTJSA-N 0.000 description 1
- SMEYEQDCCBHTEF-FXQIFTODSA-N Cys-Pro-Ala Chemical compound [H]N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O SMEYEQDCCBHTEF-FXQIFTODSA-N 0.000 description 1
- HMWBPUDETPKSSS-DCAQKATOSA-N Cys-Pro-Lys Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CS)N)C(=O)N[C@@H](CCCCN)C(=O)O HMWBPUDETPKSSS-DCAQKATOSA-N 0.000 description 1
- JUNZLDGUJZIUCO-IHRRRGAJSA-N Cys-Pro-Tyr Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CS)N)C(=O)N[C@@H](CC2=CC=C(C=C2)O)C(=O)O JUNZLDGUJZIUCO-IHRRRGAJSA-N 0.000 description 1
- XBELMDARIGXDKY-GUBZILKMSA-N Cys-Pro-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CS)N XBELMDARIGXDKY-GUBZILKMSA-N 0.000 description 1
- CMYVIUWVYHOLRD-ZLUOBGJFSA-N Cys-Ser-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O CMYVIUWVYHOLRD-ZLUOBGJFSA-N 0.000 description 1
- SRZZZTMJARUVPI-JBDRJPRFSA-N Cys-Ser-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CS)N SRZZZTMJARUVPI-JBDRJPRFSA-N 0.000 description 1
- ABLQPNMKLMFDQU-BIIVOSGPSA-N Cys-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CS)N)C(=O)O ABLQPNMKLMFDQU-BIIVOSGPSA-N 0.000 description 1
- DQGIAOGALAQBGK-BWBBJGPYSA-N Cys-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CS)N)O DQGIAOGALAQBGK-BWBBJGPYSA-N 0.000 description 1
- NDNZRWUDUMTITL-FXQIFTODSA-N Cys-Ser-Val Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O NDNZRWUDUMTITL-FXQIFTODSA-N 0.000 description 1
- MWVDDZUTWXFYHL-XKBZYTNZSA-N Cys-Thr-Gln Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CS)N)O MWVDDZUTWXFYHL-XKBZYTNZSA-N 0.000 description 1
- YFKWIIRWHGKSQQ-WFBYXXMGSA-N Cys-Trp-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CS)N YFKWIIRWHGKSQQ-WFBYXXMGSA-N 0.000 description 1
- CLEFUAZULXANBU-MELADBBJSA-N Cys-Tyr-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CS)N)C(=O)O CLEFUAZULXANBU-MELADBBJSA-N 0.000 description 1
- FCXJJTRGVAZDER-FXQIFTODSA-N Cys-Val-Ala Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O FCXJJTRGVAZDER-FXQIFTODSA-N 0.000 description 1
- ALTQTAKGRFLRLR-GUBZILKMSA-N Cys-Val-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)O)NC(=O)[C@H](CS)N ALTQTAKGRFLRLR-GUBZILKMSA-N 0.000 description 1
- 108010041986 DNA Vaccines Proteins 0.000 description 1
- 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 description 1
- 229940124087 DNA topoisomerase II inhibitor Drugs 0.000 description 1
- 229940021995 DNA vaccine Drugs 0.000 description 1
- 102000016607 Diphtheria Toxin Human genes 0.000 description 1
- 108010053187 Diphtheria Toxin Proteins 0.000 description 1
- 102000001301 EGF receptor Human genes 0.000 description 1
- 108060006698 EGF receptor Proteins 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 102100039328 Endoplasmin Human genes 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- 102100035233 Furin Human genes 0.000 description 1
- 108090001126 Furin Proteins 0.000 description 1
- HHWQMFIGMMOVFK-WDSKDSINSA-N Gln-Ala-Gly Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(N)=O HHWQMFIGMMOVFK-WDSKDSINSA-N 0.000 description 1
- ZFADFBPRMSBPOT-KKUMJFAQSA-N Gln-Arg-Phe Chemical compound N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](Cc1ccccc1)C(O)=O ZFADFBPRMSBPOT-KKUMJFAQSA-N 0.000 description 1
- INFBPLSHYFALDE-ACZMJKKPSA-N Gln-Asn-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(O)=O INFBPLSHYFALDE-ACZMJKKPSA-N 0.000 description 1
- RRYLMJWPWBJFPZ-ACZMJKKPSA-N Gln-Asn-Asp Chemical compound C(CC(=O)N)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)N RRYLMJWPWBJFPZ-ACZMJKKPSA-N 0.000 description 1
- WMOMPXKOKASNBK-PEFMBERDSA-N Gln-Asn-Ile Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O WMOMPXKOKASNBK-PEFMBERDSA-N 0.000 description 1
- CYTSBCIIEHUPDU-ACZMJKKPSA-N Gln-Asp-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O CYTSBCIIEHUPDU-ACZMJKKPSA-N 0.000 description 1
- CRRFJBGUGNNOCS-PEFMBERDSA-N Gln-Asp-Ile Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O CRRFJBGUGNNOCS-PEFMBERDSA-N 0.000 description 1
- JFSNBQJNDMXMQF-XHNCKOQMSA-N Gln-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)N)N)C(=O)O JFSNBQJNDMXMQF-XHNCKOQMSA-N 0.000 description 1
- GNDJOCGXGLNCKY-ACZMJKKPSA-N Gln-Cys-Cys Chemical compound N[C@@H](CCC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(O)=O GNDJOCGXGLNCKY-ACZMJKKPSA-N 0.000 description 1
- LPJVZYMINRLCQA-AVGNSLFASA-N Gln-Cys-Phe Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(=O)N)N LPJVZYMINRLCQA-AVGNSLFASA-N 0.000 description 1
- IVCOYUURLWQDJQ-LPEHRKFASA-N Gln-Gln-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)N)C(=O)O IVCOYUURLWQDJQ-LPEHRKFASA-N 0.000 description 1
- PXAFHUATEHLECW-GUBZILKMSA-N Gln-Glu-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)N)N PXAFHUATEHLECW-GUBZILKMSA-N 0.000 description 1
- FGYPOQPQTUNESW-IUCAKERBSA-N Gln-Gly-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCC(=O)N)N FGYPOQPQTUNESW-IUCAKERBSA-N 0.000 description 1
- SMLDOQHTOAAFJQ-WDSKDSINSA-N Gln-Gly-Ser Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CO)C(O)=O SMLDOQHTOAAFJQ-WDSKDSINSA-N 0.000 description 1
- NNXIQPMZGZUFJJ-AVGNSLFASA-N Gln-His-Lys Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)N)N NNXIQPMZGZUFJJ-AVGNSLFASA-N 0.000 description 1
- ZNTDJIMJKNNSLR-RWRJDSDZSA-N Gln-Ile-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)O)NC(=O)[C@H](CCC(=O)N)N ZNTDJIMJKNNSLR-RWRJDSDZSA-N 0.000 description 1
- VUVKKXPCKILIBD-AVGNSLFASA-N Gln-Leu-His Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CCC(=O)N)N VUVKKXPCKILIBD-AVGNSLFASA-N 0.000 description 1
- PSERKXGRRADTKA-MNXVOIDGSA-N Gln-Leu-Ile Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O PSERKXGRRADTKA-MNXVOIDGSA-N 0.000 description 1
- FTTHLXOMDMLKKW-FHWLQOOXSA-N Gln-Phe-Phe Chemical compound C([C@H](NC(=O)[C@H](CCC(N)=O)N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 FTTHLXOMDMLKKW-FHWLQOOXSA-N 0.000 description 1
- ZVQZXPADLZIQFF-FHWLQOOXSA-N Gln-Phe-Tyr Chemical compound C([C@H](NC(=O)[C@H](CCC(N)=O)N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=CC=C1 ZVQZXPADLZIQFF-FHWLQOOXSA-N 0.000 description 1
- FNAJNWPDTIXYJN-CIUDSAMLSA-N Gln-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCC(N)=O FNAJNWPDTIXYJN-CIUDSAMLSA-N 0.000 description 1
- NPMFDZGLKBNFOO-SRVKXCTJSA-N Gln-Pro-His Chemical compound NC(=O)CC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CN=CN1 NPMFDZGLKBNFOO-SRVKXCTJSA-N 0.000 description 1
- LGWNISYVKDNJRP-FXQIFTODSA-N Gln-Ser-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O LGWNISYVKDNJRP-FXQIFTODSA-N 0.000 description 1
- CVRUVYDNRPSKBM-QEJZJMRPSA-N Gln-Trp-Ser Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CCC(=O)N)N CVRUVYDNRPSKBM-QEJZJMRPSA-N 0.000 description 1
- ZZLDMBMFKZFQMU-NRPADANISA-N Gln-Val-Ala Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O ZZLDMBMFKZFQMU-NRPADANISA-N 0.000 description 1
- UTKICHUQEQBDGC-ACZMJKKPSA-N Glu-Ala-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCC(=O)O)N UTKICHUQEQBDGC-ACZMJKKPSA-N 0.000 description 1
- LKDIBBOKUAASNP-FXQIFTODSA-N Glu-Ala-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O LKDIBBOKUAASNP-FXQIFTODSA-N 0.000 description 1
- ATRHMOJQJWPVBQ-DRZSPHRISA-N Glu-Ala-Phe Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O ATRHMOJQJWPVBQ-DRZSPHRISA-N 0.000 description 1
- JPHYJQHPILOKHC-ACZMJKKPSA-N Glu-Asp-Asp Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O JPHYJQHPILOKHC-ACZMJKKPSA-N 0.000 description 1
- ZZIFPJZQHRJERU-WDSKDSINSA-N Glu-Cys-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CS)C(=O)NCC(O)=O ZZIFPJZQHRJERU-WDSKDSINSA-N 0.000 description 1
- XMVLTPMCUJTJQP-FXQIFTODSA-N Glu-Gln-Cys Chemical compound C(CC(=O)O)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CS)C(=O)O)N XMVLTPMCUJTJQP-FXQIFTODSA-N 0.000 description 1
- CGOHAEBMDSEKFB-FXQIFTODSA-N Glu-Glu-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O CGOHAEBMDSEKFB-FXQIFTODSA-N 0.000 description 1
- QJCKNLPMTPXXEM-AUTRQRHGSA-N Glu-Glu-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCC(O)=O QJCKNLPMTPXXEM-AUTRQRHGSA-N 0.000 description 1
- LRPXYSGPOBVBEH-IUCAKERBSA-N Glu-Gly-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O LRPXYSGPOBVBEH-IUCAKERBSA-N 0.000 description 1
- ZWQVYZXPYSYPJD-RYUDHWBXSA-N Glu-Gly-Phe Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ZWQVYZXPYSYPJD-RYUDHWBXSA-N 0.000 description 1
- QLPYYTDOUQNJGQ-AVGNSLFASA-N Glu-His-Lys Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CCC(=O)O)N QLPYYTDOUQNJGQ-AVGNSLFASA-N 0.000 description 1
- BKRQSECBKKCCKW-HVTMNAMFSA-N Glu-Ile-His Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CCC(=O)O)N BKRQSECBKKCCKW-HVTMNAMFSA-N 0.000 description 1
- OHWJUIXZHVIXJJ-GUBZILKMSA-N Glu-Lys-Cys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CCC(=O)O)N OHWJUIXZHVIXJJ-GUBZILKMSA-N 0.000 description 1
- RBXSZQRSEGYDFG-GUBZILKMSA-N Glu-Lys-Ser Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(O)=O RBXSZQRSEGYDFG-GUBZILKMSA-N 0.000 description 1
- KJBGAZSLZAQDPV-KKUMJFAQSA-N Glu-Phe-Arg Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CCC(=O)O)N KJBGAZSLZAQDPV-KKUMJFAQSA-N 0.000 description 1
- CBWKURKPYSLMJV-SOUVJXGZSA-N Glu-Phe-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CCC(=O)O)N)C(=O)O CBWKURKPYSLMJV-SOUVJXGZSA-N 0.000 description 1
- QJVZSVUYZFYLFQ-CIUDSAMLSA-N Glu-Pro-Ala Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O QJVZSVUYZFYLFQ-CIUDSAMLSA-N 0.000 description 1
- SYWCGQOIIARSIX-SRVKXCTJSA-N Glu-Pro-Leu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(O)=O SYWCGQOIIARSIX-SRVKXCTJSA-N 0.000 description 1
- ALMBZBOCGSVSAI-ACZMJKKPSA-N Glu-Ser-Asn Chemical compound C(CC(=O)O)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)N)C(=O)O)N ALMBZBOCGSVSAI-ACZMJKKPSA-N 0.000 description 1
- MWTGQXBHVRTCOR-GLLZPBPUSA-N Glu-Thr-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(O)=O MWTGQXBHVRTCOR-GLLZPBPUSA-N 0.000 description 1
- KXRORHJIRAOQPG-SOUVJXGZSA-N Glu-Tyr-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)[C@H](CCC(=O)O)N)C(=O)O KXRORHJIRAOQPG-SOUVJXGZSA-N 0.000 description 1
- MLILEEIVMRUYBX-NHCYSSNCSA-N Glu-Val-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O MLILEEIVMRUYBX-NHCYSSNCSA-N 0.000 description 1
- QXUPRMQJDWJDFR-NRPADANISA-N Glu-Val-Ser Chemical compound CC(C)[C@H](NC(=O)[C@@H](N)CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O QXUPRMQJDWJDFR-NRPADANISA-N 0.000 description 1
- QRWPTXLWHHTOCO-DZKIICNBSA-N Glu-Val-Tyr Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O QRWPTXLWHHTOCO-DZKIICNBSA-N 0.000 description 1
- PYTZFYUXZZHOAD-WHFBIAKZSA-N Gly-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)CN PYTZFYUXZZHOAD-WHFBIAKZSA-N 0.000 description 1
- QXPRJQPCFXMCIY-NKWVEPMBSA-N Gly-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN QXPRJQPCFXMCIY-NKWVEPMBSA-N 0.000 description 1
- QSDKBRMVXSWAQE-BFHQHQDPSA-N Gly-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)CN QSDKBRMVXSWAQE-BFHQHQDPSA-N 0.000 description 1
- XZRZILPOZBVTDB-GJZGRUSLSA-N Gly-Arg-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)CN)C(O)=O)=CNC2=C1 XZRZILPOZBVTDB-GJZGRUSLSA-N 0.000 description 1
- FMNHBTKMRFVGRO-FOHZUACHSA-N Gly-Asn-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CN FMNHBTKMRFVGRO-FOHZUACHSA-N 0.000 description 1
- IWAXHBCACVWNHT-BQBZGAKWSA-N Gly-Asp-Arg Chemical compound NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N IWAXHBCACVWNHT-BQBZGAKWSA-N 0.000 description 1
- LLXVQPKEQQCISF-YUMQZZPRSA-N Gly-Asp-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)CN LLXVQPKEQQCISF-YUMQZZPRSA-N 0.000 description 1
- NMROINAYXCACKF-WHFBIAKZSA-N Gly-Cys-Cys Chemical compound NCC(=O)N[C@@H](CS)C(=O)N[C@@H](CS)C(O)=O NMROINAYXCACKF-WHFBIAKZSA-N 0.000 description 1
- CEXINUGNTZFNRY-BYPYZUCNSA-N Gly-Cys-Gly Chemical compound [NH3+]CC(=O)N[C@@H](CS)C(=O)NCC([O-])=O CEXINUGNTZFNRY-BYPYZUCNSA-N 0.000 description 1
- YYQGVXNKAXUTJU-YUMQZZPRSA-N Gly-Cys-His Chemical compound NCC(=O)N[C@@H](CS)C(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O YYQGVXNKAXUTJU-YUMQZZPRSA-N 0.000 description 1
- UEGIPZAXNBYCCP-NKWVEPMBSA-N Gly-Cys-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CS)NC(=O)CN)C(=O)O UEGIPZAXNBYCCP-NKWVEPMBSA-N 0.000 description 1
- KTSZUNRRYXPZTK-BQBZGAKWSA-N Gly-Gln-Glu Chemical compound NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O KTSZUNRRYXPZTK-BQBZGAKWSA-N 0.000 description 1
- AQLHORCVPGXDJW-IUCAKERBSA-N Gly-Gln-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)CN AQLHORCVPGXDJW-IUCAKERBSA-N 0.000 description 1
- SOEATRRYCIPEHA-BQBZGAKWSA-N Gly-Glu-Glu Chemical compound [H]NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O SOEATRRYCIPEHA-BQBZGAKWSA-N 0.000 description 1
- YYPFZVIXAVDHIK-IUCAKERBSA-N Gly-Glu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CN YYPFZVIXAVDHIK-IUCAKERBSA-N 0.000 description 1
- YWAQATDNEKZFFK-BYPYZUCNSA-N Gly-Gly-Ser Chemical compound NCC(=O)NCC(=O)N[C@@H](CO)C(O)=O YWAQATDNEKZFFK-BYPYZUCNSA-N 0.000 description 1
- ZKLYPEGLWFVRGF-IUCAKERBSA-N Gly-His-Gln Chemical compound [H]NCC(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(N)=O)C(O)=O ZKLYPEGLWFVRGF-IUCAKERBSA-N 0.000 description 1
- FSPVILZGHUJOHS-QWRGUYRKSA-N Gly-His-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CC1=CNC=N1 FSPVILZGHUJOHS-QWRGUYRKSA-N 0.000 description 1
- HPAIKDPJURGQLN-KBPBESRZSA-N Gly-His-Phe Chemical compound C([C@H](NC(=O)CN)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CNC=N1 HPAIKDPJURGQLN-KBPBESRZSA-N 0.000 description 1
- LPCKHUXOGVNZRS-YUMQZZPRSA-N Gly-His-Ser Chemical compound [H]NCC(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(O)=O LPCKHUXOGVNZRS-YUMQZZPRSA-N 0.000 description 1
- DENRBIYENOKSEX-PEXQALLHSA-N Gly-Ile-His Chemical compound NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 DENRBIYENOKSEX-PEXQALLHSA-N 0.000 description 1
- PAWIVEIWWYGBAM-YUMQZZPRSA-N Gly-Leu-Ala Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O PAWIVEIWWYGBAM-YUMQZZPRSA-N 0.000 description 1
- NSTUFLGQJCOCDL-UWVGGRQHSA-N Gly-Leu-Arg Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N NSTUFLGQJCOCDL-UWVGGRQHSA-N 0.000 description 1
- ULZCYBYDTUMHNF-IUCAKERBSA-N Gly-Leu-Glu Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O ULZCYBYDTUMHNF-IUCAKERBSA-N 0.000 description 1
- UUYBFNKHOCJCHT-VHSXEESVSA-N Gly-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN UUYBFNKHOCJCHT-VHSXEESVSA-N 0.000 description 1
- NNCSJUBVFBDDLC-YUMQZZPRSA-N Gly-Leu-Ser Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O NNCSJUBVFBDDLC-YUMQZZPRSA-N 0.000 description 1
- MIIVFRCYJABHTQ-ONGXEEELSA-N Gly-Leu-Val Chemical compound [H]NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O MIIVFRCYJABHTQ-ONGXEEELSA-N 0.000 description 1
- MHXKHKWHPNETGG-QWRGUYRKSA-N Gly-Lys-Leu Chemical compound [H]NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O MHXKHKWHPNETGG-QWRGUYRKSA-N 0.000 description 1
- ZWRDOVYMQAAISL-UWVGGRQHSA-N Gly-Met-Lys Chemical compound CSCC[C@H](NC(=O)CN)C(=O)N[C@H](C(O)=O)CCCCN ZWRDOVYMQAAISL-UWVGGRQHSA-N 0.000 description 1
- WZSHYFGOLPXPLL-RYUDHWBXSA-N Gly-Phe-Glu Chemical compound NCC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCC(O)=O)C(O)=O WZSHYFGOLPXPLL-RYUDHWBXSA-N 0.000 description 1
- HJARVELKOSZUEW-YUMQZZPRSA-N Gly-Pro-Gln Chemical compound [H]NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(O)=O HJARVELKOSZUEW-YUMQZZPRSA-N 0.000 description 1
- BMWFDYIYBAFROD-WPRPVWTQSA-N Gly-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)CN BMWFDYIYBAFROD-WPRPVWTQSA-N 0.000 description 1
- VNNRLUNBJSWZPF-ZKWXMUAHSA-N Gly-Ser-Ile Chemical compound [H]NCC(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O VNNRLUNBJSWZPF-ZKWXMUAHSA-N 0.000 description 1
- WCORRBXVISTKQL-WHFBIAKZSA-N Gly-Ser-Ser Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O WCORRBXVISTKQL-WHFBIAKZSA-N 0.000 description 1
- JQFILXICXLDTRR-FBCQKBJTSA-N Gly-Thr-Gly Chemical compound NCC(=O)N[C@@H]([C@H](O)C)C(=O)NCC(O)=O JQFILXICXLDTRR-FBCQKBJTSA-N 0.000 description 1
- RHRLHXQWHCNJKR-PMVVWTBXSA-N Gly-Thr-His Chemical compound NCC(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CC1=CN=CN1 RHRLHXQWHCNJKR-PMVVWTBXSA-N 0.000 description 1
- ZZWUYQXMIFTIIY-WEDXCCLWSA-N Gly-Thr-Leu Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O ZZWUYQXMIFTIIY-WEDXCCLWSA-N 0.000 description 1
- XHVONGZZVUUORG-WEDXCCLWSA-N Gly-Thr-Lys Chemical compound NCC(=O)N[C@@H]([C@H](O)C)C(=O)N[C@H](C(O)=O)CCCCN XHVONGZZVUUORG-WEDXCCLWSA-N 0.000 description 1
- WSWWTQYHFCBKBT-DVJZZOLTSA-N Gly-Thr-Trp Chemical compound C[C@@H](O)[C@H](NC(=O)CN)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(O)=O WSWWTQYHFCBKBT-DVJZZOLTSA-N 0.000 description 1
- ONSARSFSJHTMFJ-STQMWFEESA-N Gly-Trp-Ser Chemical compound [H]NCC(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CO)C(O)=O ONSARSFSJHTMFJ-STQMWFEESA-N 0.000 description 1
- LYZYGGWCBLBDMC-QWHCGFSZSA-N Gly-Tyr-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)CN)C(=O)O LYZYGGWCBLBDMC-QWHCGFSZSA-N 0.000 description 1
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 1
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 description 1
- 101710083479 Hepatitis A virus cellular receptor 2 homolog Proteins 0.000 description 1
- VSLXGYMEHVAJBH-DLOVCJGASA-N His-Ala-Leu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O VSLXGYMEHVAJBH-DLOVCJGASA-N 0.000 description 1
- FLUVGKKRRMLNPU-CQDKDKBSSA-N His-Ala-Phe Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O FLUVGKKRRMLNPU-CQDKDKBSSA-N 0.000 description 1
- DZMVESFTHXSSPZ-XVYDVKMFSA-N His-Ala-Ser Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O DZMVESFTHXSSPZ-XVYDVKMFSA-N 0.000 description 1
- JBJNKUOMNZGQIM-PYJNHQTQSA-N His-Arg-Ile Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O JBJNKUOMNZGQIM-PYJNHQTQSA-N 0.000 description 1
- OHOXVDFVRDGFND-YUMQZZPRSA-N His-Cys-Gly Chemical compound N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CS)C(=O)NCC(O)=O OHOXVDFVRDGFND-YUMQZZPRSA-N 0.000 description 1
- YTKOTXRIWQHSAZ-GUBZILKMSA-N His-Glu-Cys Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CS)C(=O)O)N YTKOTXRIWQHSAZ-GUBZILKMSA-N 0.000 description 1
- FIMNVXRZGUAGBI-AVGNSLFASA-N His-Glu-Leu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O FIMNVXRZGUAGBI-AVGNSLFASA-N 0.000 description 1
- YADRBUZBKHHDAO-XPUUQOCRSA-N His-Gly-Ala Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)NCC(=O)N[C@@H](C)C(O)=O YADRBUZBKHHDAO-XPUUQOCRSA-N 0.000 description 1
- IDQNVIWPPWAFSY-AVGNSLFASA-N His-His-Gln Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(N)=O)C(O)=O IDQNVIWPPWAFSY-AVGNSLFASA-N 0.000 description 1
- UROVZOUMHNXPLZ-AVGNSLFASA-N His-Leu-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CN=CN1 UROVZOUMHNXPLZ-AVGNSLFASA-N 0.000 description 1
- AIPUZFXMXAHZKY-QWRGUYRKSA-N His-Leu-Gly Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O AIPUZFXMXAHZKY-QWRGUYRKSA-N 0.000 description 1
- BPOHQCZZSFBSON-KKUMJFAQSA-N His-Leu-His Chemical compound CC(C)C[C@H](NC(=O)[C@@H](N)Cc1cnc[nH]1)C(=O)N[C@@H](Cc1cnc[nH]1)C(O)=O BPOHQCZZSFBSON-KKUMJFAQSA-N 0.000 description 1
- RNMNYMDTESKEAJ-KKUMJFAQSA-N His-Leu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC1=CN=CN1 RNMNYMDTESKEAJ-KKUMJFAQSA-N 0.000 description 1
- BZAQOPHNBFOOJS-DCAQKATOSA-N His-Pro-Asp Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O BZAQOPHNBFOOJS-DCAQKATOSA-N 0.000 description 1
- PYNPBMCLAKTHJL-SRVKXCTJSA-N His-Pro-Glu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O PYNPBMCLAKTHJL-SRVKXCTJSA-N 0.000 description 1
- FFKJUTZARGRVTH-KKUMJFAQSA-N His-Ser-Tyr Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O FFKJUTZARGRVTH-KKUMJFAQSA-N 0.000 description 1
- MKWFGXSFLYNTKC-XIRDDKMYSA-N His-Trp-Asp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CC3=CN=CN3)N MKWFGXSFLYNTKC-XIRDDKMYSA-N 0.000 description 1
- JVEKQAYXFGIISZ-HOCLYGCPSA-N His-Trp-Gly Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(O)=O)C1=CN=CN1 JVEKQAYXFGIISZ-HOCLYGCPSA-N 0.000 description 1
- WSWAUVHXQREQQG-JYJNAYRXSA-N His-Tyr-Gln Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O WSWAUVHXQREQQG-JYJNAYRXSA-N 0.000 description 1
- FFYYUUWROYYKFY-IHRRRGAJSA-N His-Val-Leu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O FFYYUUWROYYKFY-IHRRRGAJSA-N 0.000 description 1
- MCGOGXFMKHPMSQ-AVGNSLFASA-N His-Val-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](N)CC1=CN=CN1 MCGOGXFMKHPMSQ-AVGNSLFASA-N 0.000 description 1
- FBOMZVOKCZMDIG-XQQFMLRXSA-N His-Val-Pro Chemical compound CC(C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CN=CN2)N FBOMZVOKCZMDIG-XQQFMLRXSA-N 0.000 description 1
- XGBVLRJLHUVCNK-DCAQKATOSA-N His-Val-Ser Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O XGBVLRJLHUVCNK-DCAQKATOSA-N 0.000 description 1
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 1
- 108010027412 Histocompatibility Antigens Class II Proteins 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- RWIKBYVJQAJYDP-BJDJZHNGSA-N Ile-Ala-Lys Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCCN RWIKBYVJQAJYDP-BJDJZHNGSA-N 0.000 description 1
- YOTNPRLPIPHQSB-XUXIUFHCSA-N Ile-Arg-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)O)N YOTNPRLPIPHQSB-XUXIUFHCSA-N 0.000 description 1
- LLZLRXBTOOFODM-QSFUFRPTSA-N Ile-Asp-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)O)N LLZLRXBTOOFODM-QSFUFRPTSA-N 0.000 description 1
- LOXMWQOKYBGCHF-JBDRJPRFSA-N Ile-Cys-Ala Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@@H](C)C(O)=O LOXMWQOKYBGCHF-JBDRJPRFSA-N 0.000 description 1
- FHCNLXMTQJNJNH-KBIXCLLPSA-N Ile-Cys-Gln Chemical compound N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)O FHCNLXMTQJNJNH-KBIXCLLPSA-N 0.000 description 1
- LKACSKJPTFSBHR-MNXVOIDGSA-N Ile-Gln-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O)N LKACSKJPTFSBHR-MNXVOIDGSA-N 0.000 description 1
- WUKLZPHVWAMZQV-UKJIMTQDSA-N Ile-Glu-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)O)N WUKLZPHVWAMZQV-UKJIMTQDSA-N 0.000 description 1
- KFVUBLZRFSVDGO-BYULHYEWSA-N Ile-Gly-Asp Chemical compound CC[C@H](C)[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(O)=O KFVUBLZRFSVDGO-BYULHYEWSA-N 0.000 description 1
- CMNMPCTVCWWYHY-MXAVVETBSA-N Ile-His-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](CC(C)C)C(=O)O)N CMNMPCTVCWWYHY-MXAVVETBSA-N 0.000 description 1
- HPCFRQWLTRDGHT-AJNGGQMLSA-N Ile-Leu-Leu Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O HPCFRQWLTRDGHT-AJNGGQMLSA-N 0.000 description 1
- PARSHQDZROHERM-NHCYSSNCSA-N Ile-Lys-Gly Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)O)N PARSHQDZROHERM-NHCYSSNCSA-N 0.000 description 1
- XLXPYSDGMXTTNQ-DKIMLUQUSA-N Ile-Phe-Leu Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(O)=O XLXPYSDGMXTTNQ-DKIMLUQUSA-N 0.000 description 1
- PELCGFMHLZXWBQ-BJDJZHNGSA-N Ile-Ser-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)O)N PELCGFMHLZXWBQ-BJDJZHNGSA-N 0.000 description 1
- JNLSTRPWUXOORL-MMWGEVLESA-N Ile-Ser-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N1CCC[C@@H]1C(=O)O)N JNLSTRPWUXOORL-MMWGEVLESA-N 0.000 description 1
- RKQAYOWLSFLJEE-SVSWQMSJSA-N Ile-Thr-Cys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)O)N RKQAYOWLSFLJEE-SVSWQMSJSA-N 0.000 description 1
- WRDTXMBPHMBGIB-STECZYCISA-N Ile-Tyr-Val Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C(C)C)C(O)=O)CC1=CC=C(O)C=C1 WRDTXMBPHMBGIB-STECZYCISA-N 0.000 description 1
- BCISUQVFDGYZBO-QSFUFRPTSA-N Ile-Val-Asp Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC(O)=O BCISUQVFDGYZBO-QSFUFRPTSA-N 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- IBMVEYRWAWIOTN-UHFFFAOYSA-N L-Leucyl-L-Arginyl-L-Proline Natural products CC(C)CC(N)C(=O)NC(CCCN=C(N)N)C(=O)N1CCCC1C(O)=O IBMVEYRWAWIOTN-UHFFFAOYSA-N 0.000 description 1
- HGCNKOLVKRAVHD-UHFFFAOYSA-N L-Met-L-Phe Natural products CSCCC(N)C(=O)NC(C(O)=O)CC1=CC=CC=C1 HGCNKOLVKRAVHD-UHFFFAOYSA-N 0.000 description 1
- SENJXOPIZNYLHU-UHFFFAOYSA-N L-leucyl-L-arginine Natural products CC(C)CC(N)C(=O)NC(C(O)=O)CCCN=C(N)N SENJXOPIZNYLHU-UHFFFAOYSA-N 0.000 description 1
- KFKWRHQBZQICHA-STQMWFEESA-N L-leucyl-L-phenylalanine Natural products CC(C)C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 KFKWRHQBZQICHA-STQMWFEESA-N 0.000 description 1
- LJHGALIOHLRRQN-DCAQKATOSA-N Leu-Ala-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N LJHGALIOHLRRQN-DCAQKATOSA-N 0.000 description 1
- CQQGCWPXDHTTNF-GUBZILKMSA-N Leu-Ala-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(O)=O CQQGCWPXDHTTNF-GUBZILKMSA-N 0.000 description 1
- WSGXUIQTEZDVHJ-GARJFASQSA-N Leu-Ala-Pro Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N1CCC[C@@H]1C(O)=O WSGXUIQTEZDVHJ-GARJFASQSA-N 0.000 description 1
- XBBKIIGCUMBKCO-JXUBOQSCSA-N Leu-Ala-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XBBKIIGCUMBKCO-JXUBOQSCSA-N 0.000 description 1
- SUPVSFFZWVOEOI-UHFFFAOYSA-N Leu-Ala-Tyr Natural products CC(C)CC(N)C(=O)NC(C)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 SUPVSFFZWVOEOI-UHFFFAOYSA-N 0.000 description 1
- CNNQBZRGQATKNY-DCAQKATOSA-N Leu-Arg-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CS)C(=O)O)N CNNQBZRGQATKNY-DCAQKATOSA-N 0.000 description 1
- GRZSCTXVCDUIPO-SRVKXCTJSA-N Leu-Arg-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O GRZSCTXVCDUIPO-SRVKXCTJSA-N 0.000 description 1
- RFUBXQQFJFGJFV-GUBZILKMSA-N Leu-Asn-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O RFUBXQQFJFGJFV-GUBZILKMSA-N 0.000 description 1
- OXKYZSRZKBTVEY-ZPFDUUQYSA-N Leu-Asn-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O OXKYZSRZKBTVEY-ZPFDUUQYSA-N 0.000 description 1
- YKNBJXOJTURHCU-DCAQKATOSA-N Leu-Asp-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N YKNBJXOJTURHCU-DCAQKATOSA-N 0.000 description 1
- DLFAACQHIRSQGG-CIUDSAMLSA-N Leu-Asp-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O DLFAACQHIRSQGG-CIUDSAMLSA-N 0.000 description 1
- DLCOFDAHNMMQPP-SRVKXCTJSA-N Leu-Asp-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O DLCOFDAHNMMQPP-SRVKXCTJSA-N 0.000 description 1
- MMEDVBWCMGRKKC-GARJFASQSA-N Leu-Asp-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N MMEDVBWCMGRKKC-GARJFASQSA-N 0.000 description 1
- KWURTLAFFDOTEQ-GUBZILKMSA-N Leu-Cys-Glu Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N KWURTLAFFDOTEQ-GUBZILKMSA-N 0.000 description 1
- KAFOIVJDVSZUMD-UHFFFAOYSA-N Leu-Gln-Gln Natural products CC(C)CC(N)C(=O)NC(CCC(N)=O)C(=O)NC(CCC(N)=O)C(O)=O KAFOIVJDVSZUMD-UHFFFAOYSA-N 0.000 description 1
- CQGSYZCULZMEDE-SRVKXCTJSA-N Leu-Gln-Pro Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(O)=O CQGSYZCULZMEDE-SRVKXCTJSA-N 0.000 description 1
- CQGSYZCULZMEDE-UHFFFAOYSA-N Leu-Gln-Pro Natural products CC(C)CC(N)C(=O)NC(CCC(N)=O)C(=O)N1CCCC1C(O)=O CQGSYZCULZMEDE-UHFFFAOYSA-N 0.000 description 1
- GPICTNQYKHHHTH-GUBZILKMSA-N Leu-Gln-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O GPICTNQYKHHHTH-GUBZILKMSA-N 0.000 description 1
- DZQMXBALGUHGJT-GUBZILKMSA-N Leu-Glu-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O DZQMXBALGUHGJT-GUBZILKMSA-N 0.000 description 1
- LAPSXOAUPNOINL-YUMQZZPRSA-N Leu-Gly-Asp Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(O)=O LAPSXOAUPNOINL-YUMQZZPRSA-N 0.000 description 1
- YFBBUHJJUXXZOF-UWVGGRQHSA-N Leu-Gly-Pro Chemical compound CC(C)C[C@H](N)C(=O)NCC(=O)N1CCC[C@H]1C(O)=O YFBBUHJJUXXZOF-UWVGGRQHSA-N 0.000 description 1
- VZBIUJURDLFFOE-IHRRRGAJSA-N Leu-His-Arg Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O VZBIUJURDLFFOE-IHRRRGAJSA-N 0.000 description 1
- YWYQSLOTVIRCFE-SRVKXCTJSA-N Leu-His-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(O)=O)C(O)=O YWYQSLOTVIRCFE-SRVKXCTJSA-N 0.000 description 1
- KXODZBLFVFSLAI-AVGNSLFASA-N Leu-His-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(C)C)CC1=CN=CN1 KXODZBLFVFSLAI-AVGNSLFASA-N 0.000 description 1
- XBCWOTOCBXXJDG-BZSNNMDCSA-N Leu-His-Phe Chemical compound C([C@H](NC(=O)[C@@H](N)CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CN=CN1 XBCWOTOCBXXJDG-BZSNNMDCSA-N 0.000 description 1
- SGIIOQQGLUUMDQ-IHRRRGAJSA-N Leu-His-Val Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](C(C)C)C(=O)O)N SGIIOQQGLUUMDQ-IHRRRGAJSA-N 0.000 description 1
- DBSLVQBXKVKDKJ-BJDJZHNGSA-N Leu-Ile-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O DBSLVQBXKVKDKJ-BJDJZHNGSA-N 0.000 description 1
- ORWTWZXGDBYVCP-BJDJZHNGSA-N Leu-Ile-Cys Chemical compound SC[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CC(C)C ORWTWZXGDBYVCP-BJDJZHNGSA-N 0.000 description 1
- IFMPDNRWZZEZSL-SRVKXCTJSA-N Leu-Leu-Cys Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(O)=O IFMPDNRWZZEZSL-SRVKXCTJSA-N 0.000 description 1
- FAELBUXXFQLUAX-AJNGGQMLSA-N Leu-Leu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(C)C FAELBUXXFQLUAX-AJNGGQMLSA-N 0.000 description 1
- DCGXHWINSHEPIR-SRVKXCTJSA-N Leu-Lys-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)O)N DCGXHWINSHEPIR-SRVKXCTJSA-N 0.000 description 1
- OVZLLFONXILPDZ-VOAKCMCISA-N Leu-Lys-Thr Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OVZLLFONXILPDZ-VOAKCMCISA-N 0.000 description 1
- KQFZKDITNUEVFJ-JYJNAYRXSA-N Leu-Phe-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(C)C)CC1=CC=CC=C1 KQFZKDITNUEVFJ-JYJNAYRXSA-N 0.000 description 1
- SYRTUBLKWNDSDK-DKIMLUQUSA-N Leu-Phe-Ile Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O SYRTUBLKWNDSDK-DKIMLUQUSA-N 0.000 description 1
- FYPWFNKQVVEELI-ULQDDVLXSA-N Leu-Phe-Val Chemical compound CC(C)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](C(C)C)C(O)=O)CC1=CC=CC=C1 FYPWFNKQVVEELI-ULQDDVLXSA-N 0.000 description 1
- QMKFDEUJGYNFMC-AVGNSLFASA-N Leu-Pro-Arg Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(O)=O QMKFDEUJGYNFMC-AVGNSLFASA-N 0.000 description 1
- HGUUMQWGYCVPKG-DCAQKATOSA-N Leu-Pro-Cys Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CS)C(=O)O)N HGUUMQWGYCVPKG-DCAQKATOSA-N 0.000 description 1
- VULJUQZPSOASBZ-SRVKXCTJSA-N Leu-Pro-Glu Chemical compound [H]N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O VULJUQZPSOASBZ-SRVKXCTJSA-N 0.000 description 1
- XXXXOVFBXRERQL-ULQDDVLXSA-N Leu-Pro-Phe Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 XXXXOVFBXRERQL-ULQDDVLXSA-N 0.000 description 1
- CHJKEDSZNSONPS-DCAQKATOSA-N Leu-Pro-Ser Chemical compound [H]N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O CHJKEDSZNSONPS-DCAQKATOSA-N 0.000 description 1
- AKVBOOKXVAMKSS-GUBZILKMSA-N Leu-Ser-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O AKVBOOKXVAMKSS-GUBZILKMSA-N 0.000 description 1
- FGZVGOAAROXFAB-IXOXFDKPSA-N Leu-Thr-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CC(C)C)N)O FGZVGOAAROXFAB-IXOXFDKPSA-N 0.000 description 1
- KLSUAWUZBMAZCL-RHYQMDGZSA-N Leu-Thr-Pro Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(O)=O KLSUAWUZBMAZCL-RHYQMDGZSA-N 0.000 description 1
- HOMFINRJHIIZNJ-HOCLYGCPSA-N Leu-Trp-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)NCC(O)=O HOMFINRJHIIZNJ-HOCLYGCPSA-N 0.000 description 1
- UFPLDOKWDNTTRP-ULQDDVLXSA-N Leu-Tyr-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(C)C)CC1=CC=C(O)C=C1 UFPLDOKWDNTTRP-ULQDDVLXSA-N 0.000 description 1
- FBNPMTNBFFAMMH-AVGNSLFASA-N Leu-Val-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCN=C(N)N FBNPMTNBFFAMMH-AVGNSLFASA-N 0.000 description 1
- VKVDRTGWLVZJOM-DCAQKATOSA-N Leu-Val-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O VKVDRTGWLVZJOM-DCAQKATOSA-N 0.000 description 1
- 108060001084 Luciferase Proteins 0.000 description 1
- 239000005089 Luciferase Substances 0.000 description 1
- KCXUCYYZNZFGLL-SRVKXCTJSA-N Lys-Ala-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(O)=O KCXUCYYZNZFGLL-SRVKXCTJSA-N 0.000 description 1
- YIBOAHAOAWACDK-QEJZJMRPSA-N Lys-Ala-Phe Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 YIBOAHAOAWACDK-QEJZJMRPSA-N 0.000 description 1
- NQCJGQHHYZNUDK-DCAQKATOSA-N Lys-Arg-Ser Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CO)C(O)=O)CCCN=C(N)N NQCJGQHHYZNUDK-DCAQKATOSA-N 0.000 description 1
- HQVDJTYKCMIWJP-YUMQZZPRSA-N Lys-Asn-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O HQVDJTYKCMIWJP-YUMQZZPRSA-N 0.000 description 1
- OVIVOCSURJYCTM-GUBZILKMSA-N Lys-Asp-Glu Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCC(O)=O OVIVOCSURJYCTM-GUBZILKMSA-N 0.000 description 1
- AAORVPFVUIHEAB-YUMQZZPRSA-N Lys-Asp-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(O)=O AAORVPFVUIHEAB-YUMQZZPRSA-N 0.000 description 1
- QIJVAFLRMVBHMU-KKUMJFAQSA-N Lys-Asp-Phe Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O QIJVAFLRMVBHMU-KKUMJFAQSA-N 0.000 description 1
- PRSBSVAVOQOAMI-BJDJZHNGSA-N Lys-Ile-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CCCCN PRSBSVAVOQOAMI-BJDJZHNGSA-N 0.000 description 1
- AIRZWUMAHCDDHR-KKUMJFAQSA-N Lys-Leu-Leu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O AIRZWUMAHCDDHR-KKUMJFAQSA-N 0.000 description 1
- WRODMZBHNNPRLN-SRVKXCTJSA-N Lys-Leu-Ser Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O WRODMZBHNNPRLN-SRVKXCTJSA-N 0.000 description 1
- PFZWARWVRNTPBR-IHPCNDPISA-N Lys-Leu-Trp Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CCCCN)N PFZWARWVRNTPBR-IHPCNDPISA-N 0.000 description 1
- LJADEBULDNKJNK-IHRRRGAJSA-N Lys-Leu-Val Chemical compound CC(C)C[C@H](NC(=O)[C@@H](N)CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O LJADEBULDNKJNK-IHRRRGAJSA-N 0.000 description 1
- PYFNONMJYNJENN-AVGNSLFASA-N Lys-Lys-Gln Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N PYFNONMJYNJENN-AVGNSLFASA-N 0.000 description 1
- BEGQVWUZFXLNHZ-IHPCNDPISA-N Lys-Lys-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCCN)C(O)=O)=CNC2=C1 BEGQVWUZFXLNHZ-IHPCNDPISA-N 0.000 description 1
- IPSDPDAOSAEWCN-RHYQMDGZSA-N Lys-Met-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O IPSDPDAOSAEWCN-RHYQMDGZSA-N 0.000 description 1
- ZJSZPXISKMDJKQ-JYJNAYRXSA-N Lys-Phe-Glu Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(O)=O)CC1=CC=CC=C1 ZJSZPXISKMDJKQ-JYJNAYRXSA-N 0.000 description 1
- CTJUSALVKAWFFU-CIUDSAMLSA-N Lys-Ser-Cys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N CTJUSALVKAWFFU-CIUDSAMLSA-N 0.000 description 1
- MEQLGHAMAUPOSJ-DCAQKATOSA-N Lys-Ser-Val Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O MEQLGHAMAUPOSJ-DCAQKATOSA-N 0.000 description 1
- 108010066345 MHC binding peptide Proteins 0.000 description 1
- 206010027406 Mesothelioma Diseases 0.000 description 1
- QRHWTCJBCLGYRB-FXQIFTODSA-N Met-Ala-Cys Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CS)C(O)=O QRHWTCJBCLGYRB-FXQIFTODSA-N 0.000 description 1
- GAELMDJMQDUDLJ-BQBZGAKWSA-N Met-Ala-Gly Chemical compound CSCC[C@H](N)C(=O)N[C@@H](C)C(=O)NCC(O)=O GAELMDJMQDUDLJ-BQBZGAKWSA-N 0.000 description 1
- DNDVVILEHVMWIS-LPEHRKFASA-N Met-Asp-Pro Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N DNDVVILEHVMWIS-LPEHRKFASA-N 0.000 description 1
- FVKRQMQQFGBXHV-QXEWZRGKSA-N Met-Asp-Val Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O FVKRQMQQFGBXHV-QXEWZRGKSA-N 0.000 description 1
- NCFZHKMKRCYQBJ-CIUDSAMLSA-N Met-Cys-Gln Chemical compound CSCC[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N NCFZHKMKRCYQBJ-CIUDSAMLSA-N 0.000 description 1
- UYAKZHGIPRCGPF-CIUDSAMLSA-N Met-Glu-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)N UYAKZHGIPRCGPF-CIUDSAMLSA-N 0.000 description 1
- GPAHWYRSHCKICP-GUBZILKMSA-N Met-Glu-Glu Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O GPAHWYRSHCKICP-GUBZILKMSA-N 0.000 description 1
- SJDQOYTYNGZZJX-SRVKXCTJSA-N Met-Glu-Leu Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O SJDQOYTYNGZZJX-SRVKXCTJSA-N 0.000 description 1
- OOSPRDCGTLQLBP-NHCYSSNCSA-N Met-Glu-Val Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O OOSPRDCGTLQLBP-NHCYSSNCSA-N 0.000 description 1
- WXJLBSXNUHIGSS-OSUNSFLBSA-N Met-Thr-Ile Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O WXJLBSXNUHIGSS-OSUNSFLBSA-N 0.000 description 1
- QQPMHUCGDRJFQK-RHYQMDGZSA-N Met-Thr-Leu Chemical compound CSCC[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CC(C)C QQPMHUCGDRJFQK-RHYQMDGZSA-N 0.000 description 1
- ZBLSZPYQQRIHQU-RCWTZXSCSA-N Met-Thr-Val Chemical compound CSCC[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O ZBLSZPYQQRIHQU-RCWTZXSCSA-N 0.000 description 1
- OOXVBECOTYHTCK-WDSOQIARSA-N Met-Trp-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CCSC)N OOXVBECOTYHTCK-WDSOQIARSA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- WUGMRIBZSVSJNP-UHFFFAOYSA-N N-L-alanyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)C(N)C)C(O)=O)=CNC2=C1 WUGMRIBZSVSJNP-UHFFFAOYSA-N 0.000 description 1
- 125000003047 N-acetyl group Chemical group 0.000 description 1
- 108700015872 N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine Proteins 0.000 description 1
- 108700020354 N-acetylmuramyl-threonyl-isoglutamine Proteins 0.000 description 1
- 230000004988 N-glycosylation Effects 0.000 description 1
- AJHCSUXXECOXOY-UHFFFAOYSA-N N-glycyl-L-tryptophan Natural products C1=CC=C2C(CC(NC(=O)CN)C(O)=O)=CNC2=C1 AJHCSUXXECOXOY-UHFFFAOYSA-N 0.000 description 1
- 108010079364 N-glycylalanine Proteins 0.000 description 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
- 108010047562 NGR peptide Proteins 0.000 description 1
- 241000208125 Nicotiana Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 108091092724 Noncoding DNA Proteins 0.000 description 1
- 108700001237 Nucleic Acid-Based Vaccines Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 101710116435 Outer membrane protein Proteins 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- WSXKXSBOJXEZDV-DLOVCJGASA-N Phe-Ala-Asn Chemical compound NC(=O)C[C@@H](C([O-])=O)NC(=O)[C@H](C)NC(=O)[C@@H]([NH3+])CC1=CC=CC=C1 WSXKXSBOJXEZDV-DLOVCJGASA-N 0.000 description 1
- CGOMLCQJEMWMCE-STQMWFEESA-N Phe-Arg-Gly Chemical compound NC(N)=NCCC[C@@H](C(=O)NCC(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 CGOMLCQJEMWMCE-STQMWFEESA-N 0.000 description 1
- AGYXCMYVTBYGCT-ULQDDVLXSA-N Phe-Arg-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(O)=O AGYXCMYVTBYGCT-ULQDDVLXSA-N 0.000 description 1
- QCHNRQQVLJYDSI-DLOVCJGASA-N Phe-Asn-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 QCHNRQQVLJYDSI-DLOVCJGASA-N 0.000 description 1
- WMGVYPPIMZPWPN-SRVKXCTJSA-N Phe-Asp-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N WMGVYPPIMZPWPN-SRVKXCTJSA-N 0.000 description 1
- IQXOZIDWLZYYAW-IHRRRGAJSA-N Phe-Asp-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)N IQXOZIDWLZYYAW-IHRRRGAJSA-N 0.000 description 1
- GDBOREPXIRKSEQ-FHWLQOOXSA-N Phe-Gln-Phe Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O GDBOREPXIRKSEQ-FHWLQOOXSA-N 0.000 description 1
- MGBRZXXGQBAULP-DRZSPHRISA-N Phe-Glu-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 MGBRZXXGQBAULP-DRZSPHRISA-N 0.000 description 1
- FMMIYCMOVGXZIP-AVGNSLFASA-N Phe-Glu-Asn Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O FMMIYCMOVGXZIP-AVGNSLFASA-N 0.000 description 1
- WPTYDQPGBMDUBI-QWRGUYRKSA-N Phe-Gly-Asn Chemical compound N[C@@H](Cc1ccccc1)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O WPTYDQPGBMDUBI-QWRGUYRKSA-N 0.000 description 1
- SFKOEHXABNPLRT-KBPBESRZSA-N Phe-His-Gly Chemical compound N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)NCC(O)=O SFKOEHXABNPLRT-KBPBESRZSA-N 0.000 description 1
- ZKSLXIGKRJMALF-MGHWNKPDSA-N Phe-His-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CC2=CC=CC=C2)N ZKSLXIGKRJMALF-MGHWNKPDSA-N 0.000 description 1
- BEEVXUYVEHXWRQ-YESZJQIVSA-N Phe-His-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CN=CN2)NC(=O)[C@H](CC3=CC=CC=C3)N)C(=O)O BEEVXUYVEHXWRQ-YESZJQIVSA-N 0.000 description 1
- SPXWRYVHOZVYBU-ULQDDVLXSA-N Phe-His-Val Chemical compound CC(C)[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CC2=CC=CC=C2)N SPXWRYVHOZVYBU-ULQDDVLXSA-N 0.000 description 1
- OSBADCBXAMSPQD-YESZJQIVSA-N Phe-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CC=CC=C2)N OSBADCBXAMSPQD-YESZJQIVSA-N 0.000 description 1
- JKJSIYKSGIDHPM-WBAXXEDZSA-N Phe-Phe-Ala Chemical compound C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](N)Cc1ccccc1)C(O)=O JKJSIYKSGIDHPM-WBAXXEDZSA-N 0.000 description 1
- MMJJFXWMCMJMQA-STQMWFEESA-N Phe-Pro-Gly Chemical compound C([C@H](N)C(=O)N1[C@@H](CCC1)C(=O)NCC(O)=O)C1=CC=CC=C1 MMJJFXWMCMJMQA-STQMWFEESA-N 0.000 description 1
- CKJACGQPCPMWIT-UFYCRDLUSA-N Phe-Pro-Phe Chemical compound C([C@H](N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CKJACGQPCPMWIT-UFYCRDLUSA-N 0.000 description 1
- NJJBATPLUQHRBM-IHRRRGAJSA-N Phe-Pro-Ser Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CC2=CC=CC=C2)N)C(=O)N[C@@H](CO)C(=O)O NJJBATPLUQHRBM-IHRRRGAJSA-N 0.000 description 1
- JXQVYPWVGUOIDV-MXAVVETBSA-N Phe-Ser-Ile Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O JXQVYPWVGUOIDV-MXAVVETBSA-N 0.000 description 1
- UNBFGVQVQGXXCK-KKUMJFAQSA-N Phe-Ser-Leu Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(O)=O UNBFGVQVQGXXCK-KKUMJFAQSA-N 0.000 description 1
- IPFXYNKCXYGSSV-KKUMJFAQSA-N Phe-Ser-Lys Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)O)N IPFXYNKCXYGSSV-KKUMJFAQSA-N 0.000 description 1
- MCIXMYKSPQUMJG-SRVKXCTJSA-N Phe-Ser-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(O)=O MCIXMYKSPQUMJG-SRVKXCTJSA-N 0.000 description 1
- MVIJMIZJPHQGEN-IHRRRGAJSA-N Phe-Ser-Val Chemical compound CC(C)[C@@H](C([O-])=O)NC(=O)[C@H](CO)NC(=O)[C@@H]([NH3+])CC1=CC=CC=C1 MVIJMIZJPHQGEN-IHRRRGAJSA-N 0.000 description 1
- BPIMVBKDLSBKIJ-FCLVOEFKSA-N Phe-Thr-Phe Chemical compound C([C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 BPIMVBKDLSBKIJ-FCLVOEFKSA-N 0.000 description 1
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
- IWNOFCGBMSFTBC-CIUDSAMLSA-N Pro-Ala-Glu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O IWNOFCGBMSFTBC-CIUDSAMLSA-N 0.000 description 1
- DRVIASBABBMZTF-GUBZILKMSA-N Pro-Ala-Met Chemical compound C[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@@H]1CCCN1 DRVIASBABBMZTF-GUBZILKMSA-N 0.000 description 1
- ICTZKEXYDDZZFP-SRVKXCTJSA-N Pro-Arg-Pro Chemical compound N([C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(O)=O)C(=O)[C@@H]1CCCN1 ICTZKEXYDDZZFP-SRVKXCTJSA-N 0.000 description 1
- XWYXZPHPYKRYPA-GMOBBJLQSA-N Pro-Asn-Ile Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O XWYXZPHPYKRYPA-GMOBBJLQSA-N 0.000 description 1
- ZCXQTRXYZOSGJR-FXQIFTODSA-N Pro-Asp-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O ZCXQTRXYZOSGJR-FXQIFTODSA-N 0.000 description 1
- DEDANIDYQAPTFI-IHRRRGAJSA-N Pro-Asp-Tyr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O DEDANIDYQAPTFI-IHRRRGAJSA-N 0.000 description 1
- GQLOZEMWEBDEAY-NAKRPEOUSA-N Pro-Cys-Ile Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O GQLOZEMWEBDEAY-NAKRPEOUSA-N 0.000 description 1
- YKQNVTOIYFQMLW-IHRRRGAJSA-N Pro-Cys-Tyr Chemical compound C([C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H]1NCCC1)C1=CC=C(O)C=C1 YKQNVTOIYFQMLW-IHRRRGAJSA-N 0.000 description 1
- YSUZKYSRAFNLRB-ULQDDVLXSA-N Pro-Gln-Trp Chemical compound N([C@@H](CCC(=O)N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)C(=O)[C@@H]1CCCN1 YSUZKYSRAFNLRB-ULQDDVLXSA-N 0.000 description 1
- LHALYDBUDCWMDY-CIUDSAMLSA-N Pro-Glu-Ala Chemical compound C[C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]1CCCN1)C(O)=O LHALYDBUDCWMDY-CIUDSAMLSA-N 0.000 description 1
- QCARZLHECSFOGG-CIUDSAMLSA-N Pro-Glu-Cys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CS)C(=O)O QCARZLHECSFOGG-CIUDSAMLSA-N 0.000 description 1
- DXTOOBDIIAJZBJ-BQBZGAKWSA-N Pro-Gly-Ser Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CO)C(O)=O DXTOOBDIIAJZBJ-BQBZGAKWSA-N 0.000 description 1
- AFXCXDQNRXTSBD-FJXKBIBVSA-N Pro-Gly-Thr Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(O)=O AFXCXDQNRXTSBD-FJXKBIBVSA-N 0.000 description 1
- BBFRBZYKHIKFBX-GMOBBJLQSA-N Pro-Ile-Asn Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@@H]1CCCN1 BBFRBZYKHIKFBX-GMOBBJLQSA-N 0.000 description 1
- BWCZJGJKOFUUCN-ZPFDUUQYSA-N Pro-Ile-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(O)=O BWCZJGJKOFUUCN-ZPFDUUQYSA-N 0.000 description 1
- KWMUAKQOVYCQJQ-ZPFDUUQYSA-N Pro-Ile-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@@H]1CCCN1 KWMUAKQOVYCQJQ-ZPFDUUQYSA-N 0.000 description 1
- UREQLMJCKFLLHM-NAKRPEOUSA-N Pro-Ile-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(O)=O UREQLMJCKFLLHM-NAKRPEOUSA-N 0.000 description 1
- RYJRPPUATSKNAY-STECZYCISA-N Pro-Ile-Tyr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)NC(=O)[C@@H]2CCCN2 RYJRPPUATSKNAY-STECZYCISA-N 0.000 description 1
- RUDOLGWDSKQQFF-DCAQKATOSA-N Pro-Leu-Asn Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O RUDOLGWDSKQQFF-DCAQKATOSA-N 0.000 description 1
- NFLNBHLMLYALOO-DCAQKATOSA-N Pro-Leu-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@@H]1CCCN1 NFLNBHLMLYALOO-DCAQKATOSA-N 0.000 description 1
- BRJGUPWVFXKBQI-XUXIUFHCSA-N Pro-Leu-Ile Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O BRJGUPWVFXKBQI-XUXIUFHCSA-N 0.000 description 1
- FKYKZHOKDOPHSA-DCAQKATOSA-N Pro-Leu-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O FKYKZHOKDOPHSA-DCAQKATOSA-N 0.000 description 1
- VTFXTWDFPTWNJY-RHYQMDGZSA-N Pro-Leu-Thr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O VTFXTWDFPTWNJY-RHYQMDGZSA-N 0.000 description 1
- SUENWIFTSTWUKD-AVGNSLFASA-N Pro-Leu-Val Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O SUENWIFTSTWUKD-AVGNSLFASA-N 0.000 description 1
- NTXFLJULRHQMDC-GUBZILKMSA-N Pro-Met-Asp Chemical compound CSCC[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@@H]1CCCN1 NTXFLJULRHQMDC-GUBZILKMSA-N 0.000 description 1
- ZJXXCGZFYQQETF-CYDGBPFRSA-N Pro-Met-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@@H]1CCCN1 ZJXXCGZFYQQETF-CYDGBPFRSA-N 0.000 description 1
- QGLFRQCECIWXFA-RCWTZXSCSA-N Pro-Met-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@@H]1CCCN1)O QGLFRQCECIWXFA-RCWTZXSCSA-N 0.000 description 1
- VGVCNKSUVSZEIE-IHRRRGAJSA-N Pro-Phe-Asn Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(N)=O)C(O)=O VGVCNKSUVSZEIE-IHRRRGAJSA-N 0.000 description 1
- NAIPAPCKKRCMBL-JYJNAYRXSA-N Pro-Pro-Phe Chemical compound C([C@@H](C(=O)O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1NCCC1)C1=CC=CC=C1 NAIPAPCKKRCMBL-JYJNAYRXSA-N 0.000 description 1
- SBVPYBFMIGDIDX-SRVKXCTJSA-N Pro-Pro-Pro Chemical compound OC(=O)[C@@H]1CCCN1C(=O)[C@H]1N(C(=O)[C@H]2NCCC2)CCC1 SBVPYBFMIGDIDX-SRVKXCTJSA-N 0.000 description 1
- FDMKYQQYJKYCLV-GUBZILKMSA-N Pro-Pro-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 FDMKYQQYJKYCLV-GUBZILKMSA-N 0.000 description 1
- KBUAPZAZPWNYSW-SRVKXCTJSA-N Pro-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 KBUAPZAZPWNYSW-SRVKXCTJSA-N 0.000 description 1
- GMJDSFYVTAMIBF-FXQIFTODSA-N Pro-Ser-Asp Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O GMJDSFYVTAMIBF-FXQIFTODSA-N 0.000 description 1
- SNGZLPOXVRTNMB-LPEHRKFASA-N Pro-Ser-Pro Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CO)C(=O)N2CCC[C@@H]2C(=O)O SNGZLPOXVRTNMB-LPEHRKFASA-N 0.000 description 1
- MKGIILKDUGDRRO-FXQIFTODSA-N Pro-Ser-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1 MKGIILKDUGDRRO-FXQIFTODSA-N 0.000 description 1
- FDMCIBSQRKFSTJ-RHYQMDGZSA-N Pro-Thr-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O FDMCIBSQRKFSTJ-RHYQMDGZSA-N 0.000 description 1
- JDJMFMVVJHLWDP-UNQGMJICSA-N Pro-Thr-Phe Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O JDJMFMVVJHLWDP-UNQGMJICSA-N 0.000 description 1
- RMJZWERKFFNNNS-XGEHTFHBSA-N Pro-Thr-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O RMJZWERKFFNNNS-XGEHTFHBSA-N 0.000 description 1
- VPBQDHMASPJHGY-JYJNAYRXSA-N Pro-Trp-Ser Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)N[C@@H](CO)C(=O)O VPBQDHMASPJHGY-JYJNAYRXSA-N 0.000 description 1
- XDKKMRPRRCOELJ-GUBZILKMSA-N Pro-Val-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 XDKKMRPRRCOELJ-GUBZILKMSA-N 0.000 description 1
- JXVXYRZQIUPYSA-NHCYSSNCSA-N Pro-Val-Gln Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O JXVXYRZQIUPYSA-NHCYSSNCSA-N 0.000 description 1
- KHRLUIPIMIQFGT-AVGNSLFASA-N Pro-Val-Leu Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O KHRLUIPIMIQFGT-AVGNSLFASA-N 0.000 description 1
- XRGIDCGRSSWCKE-SRVKXCTJSA-N Pro-Val-Met Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCSC)C(O)=O XRGIDCGRSSWCKE-SRVKXCTJSA-N 0.000 description 1
- FHJQROWZEJFZPO-SRVKXCTJSA-N Pro-Val-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]1CCCN1 FHJQROWZEJFZPO-SRVKXCTJSA-N 0.000 description 1
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 1
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 1
- 108010079005 RDV peptide Proteins 0.000 description 1
- 229940022005 RNA vaccine Drugs 0.000 description 1
- 108010025216 RVF peptide Proteins 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- MWMKFWJYRRGXOR-ZLUOBGJFSA-N Ser-Ala-Asn Chemical compound N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)O)CC(N)=O)C)CO MWMKFWJYRRGXOR-ZLUOBGJFSA-N 0.000 description 1
- BKOKTRCZXRIQPX-ZLUOBGJFSA-N Ser-Ala-Cys Chemical compound C[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CO)N BKOKTRCZXRIQPX-ZLUOBGJFSA-N 0.000 description 1
- HQTKVSCNCDLXSX-BQBZGAKWSA-N Ser-Arg-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O HQTKVSCNCDLXSX-BQBZGAKWSA-N 0.000 description 1
- OYEDZGNMSBZCIM-XGEHTFHBSA-N Ser-Arg-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O OYEDZGNMSBZCIM-XGEHTFHBSA-N 0.000 description 1
- WXWDPFVKQRVJBJ-CIUDSAMLSA-N Ser-Asn-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CO)N WXWDPFVKQRVJBJ-CIUDSAMLSA-N 0.000 description 1
- CTRHXXXHUJTTRZ-ZLUOBGJFSA-N Ser-Asp-Cys Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CO)N)C(=O)O CTRHXXXHUJTTRZ-ZLUOBGJFSA-N 0.000 description 1
- OLIJLNWFEQEFDM-SRVKXCTJSA-N Ser-Asp-Phe Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 OLIJLNWFEQEFDM-SRVKXCTJSA-N 0.000 description 1
- RNFKSBPHLTZHLU-WHFBIAKZSA-N Ser-Cys-Gly Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)NCC(=O)O)N)O RNFKSBPHLTZHLU-WHFBIAKZSA-N 0.000 description 1
- WKLJLEXEENIYQE-SRVKXCTJSA-N Ser-Cys-Tyr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O WKLJLEXEENIYQE-SRVKXCTJSA-N 0.000 description 1
- OJPHFSOMBZKQKQ-GUBZILKMSA-N Ser-Gln-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CO OJPHFSOMBZKQKQ-GUBZILKMSA-N 0.000 description 1
- KJMOINFQVCCSDX-XKBZYTNZSA-N Ser-Gln-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KJMOINFQVCCSDX-XKBZYTNZSA-N 0.000 description 1
- DGPGKMKUNGKHPK-QEJZJMRPSA-N Ser-Gln-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CO)N DGPGKMKUNGKHPK-QEJZJMRPSA-N 0.000 description 1
- SMIDBHKWSYUBRZ-ACZMJKKPSA-N Ser-Glu-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O SMIDBHKWSYUBRZ-ACZMJKKPSA-N 0.000 description 1
- GZBKRJVCRMZAST-XKBZYTNZSA-N Ser-Glu-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GZBKRJVCRMZAST-XKBZYTNZSA-N 0.000 description 1
- IXCHOHLPHNGFTJ-YUMQZZPRSA-N Ser-Gly-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CO)N IXCHOHLPHNGFTJ-YUMQZZPRSA-N 0.000 description 1
- CXBFHZLODKPIJY-AAEUAGOBSA-N Ser-Gly-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CO)N CXBFHZLODKPIJY-AAEUAGOBSA-N 0.000 description 1
- CAOYHZOWXFFAIR-CIUDSAMLSA-N Ser-His-Ser Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(O)=O CAOYHZOWXFFAIR-CIUDSAMLSA-N 0.000 description 1
- WEQAYODCJHZSJZ-KKUMJFAQSA-N Ser-His-Tyr Chemical compound C([C@H](NC(=O)[C@H](CO)N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CN=CN1 WEQAYODCJHZSJZ-KKUMJFAQSA-N 0.000 description 1
- SFTZTYBXIXLRGQ-JBDRJPRFSA-N Ser-Ile-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O SFTZTYBXIXLRGQ-JBDRJPRFSA-N 0.000 description 1
- MOINZPRHJGTCHZ-MMWGEVLESA-N Ser-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N MOINZPRHJGTCHZ-MMWGEVLESA-N 0.000 description 1
- FUMGHWDRRFCKEP-CIUDSAMLSA-N Ser-Leu-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O FUMGHWDRRFCKEP-CIUDSAMLSA-N 0.000 description 1
- UBRMZSHOOIVJPW-SRVKXCTJSA-N Ser-Leu-Lys Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(O)=O UBRMZSHOOIVJPW-SRVKXCTJSA-N 0.000 description 1
- IXZHZUGGKLRHJD-DCAQKATOSA-N Ser-Leu-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O IXZHZUGGKLRHJD-DCAQKATOSA-N 0.000 description 1
- GVMUJUPXFQFBBZ-GUBZILKMSA-N Ser-Lys-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(O)=O GVMUJUPXFQFBBZ-GUBZILKMSA-N 0.000 description 1
- OWCVUSJMEBGMOK-YUMQZZPRSA-N Ser-Lys-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O OWCVUSJMEBGMOK-YUMQZZPRSA-N 0.000 description 1
- LRZLZIUXQBIWTB-KATARQTJSA-N Ser-Lys-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O LRZLZIUXQBIWTB-KATARQTJSA-N 0.000 description 1
- KJKQUQXDEKMPDK-FXQIFTODSA-N Ser-Met-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(O)=O KJKQUQXDEKMPDK-FXQIFTODSA-N 0.000 description 1
- ZGFRMNZZTOVBOU-CIUDSAMLSA-N Ser-Met-Gln Chemical compound N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(N)=O)C(=O)O ZGFRMNZZTOVBOU-CIUDSAMLSA-N 0.000 description 1
- QMCDMHWAKMUGJE-IHRRRGAJSA-N Ser-Phe-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O QMCDMHWAKMUGJE-IHRRRGAJSA-N 0.000 description 1
- ADJDNJCSPNFFPI-FXQIFTODSA-N Ser-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CO ADJDNJCSPNFFPI-FXQIFTODSA-N 0.000 description 1
- DINQYZRMXGWWTG-GUBZILKMSA-N Ser-Pro-Pro Chemical compound OC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 DINQYZRMXGWWTG-GUBZILKMSA-N 0.000 description 1
- CKDXFSPMIDSMGV-GUBZILKMSA-N Ser-Pro-Val Chemical compound [H]N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O CKDXFSPMIDSMGV-GUBZILKMSA-N 0.000 description 1
- KQNDIKOYWZTZIX-FXQIFTODSA-N Ser-Ser-Arg Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCNC(N)=N KQNDIKOYWZTZIX-FXQIFTODSA-N 0.000 description 1
- VFWQQZMRKFOGLE-ZLUOBGJFSA-N Ser-Ser-Cys Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)O)N)O VFWQQZMRKFOGLE-ZLUOBGJFSA-N 0.000 description 1
- SRSPTFBENMJHMR-WHFBIAKZSA-N Ser-Ser-Gly Chemical compound OC[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O SRSPTFBENMJHMR-WHFBIAKZSA-N 0.000 description 1
- VGQVAVQWKJLIRM-FXQIFTODSA-N Ser-Ser-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O VGQVAVQWKJLIRM-FXQIFTODSA-N 0.000 description 1
- WUXCHQZLUHBSDJ-LKXGYXEUSA-N Ser-Thr-Asp Chemical compound OC[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(=O)N[C@@H](CC(O)=O)C(O)=O WUXCHQZLUHBSDJ-LKXGYXEUSA-N 0.000 description 1
- DYEGLQRVMBWQLD-IXOXFDKPSA-N Ser-Thr-Phe Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)O)NC(=O)[C@H](CO)N)O DYEGLQRVMBWQLD-IXOXFDKPSA-N 0.000 description 1
- ZSDXEKUKQAKZFE-XAVMHZPKSA-N Ser-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CO)N)O ZSDXEKUKQAKZFE-XAVMHZPKSA-N 0.000 description 1
- SGZVZUCRAVSPKQ-FXQIFTODSA-N Ser-Val-Cys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CO)N SGZVZUCRAVSPKQ-FXQIFTODSA-N 0.000 description 1
- LLSLRQOEAFCZLW-NRPADANISA-N Ser-Val-Gln Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O LLSLRQOEAFCZLW-NRPADANISA-N 0.000 description 1
- SYCFMSYTIFXWAJ-DCAQKATOSA-N Ser-Val-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CO)N SYCFMSYTIFXWAJ-DCAQKATOSA-N 0.000 description 1
- LGIMRDKGABDMBN-DCAQKATOSA-N Ser-Val-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CO)N LGIMRDKGABDMBN-DCAQKATOSA-N 0.000 description 1
- HSWXBJCBYSWBPT-GUBZILKMSA-N Ser-Val-Val Chemical compound CC(C)[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CO)C(C)C)C(O)=O HSWXBJCBYSWBPT-GUBZILKMSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229940126547 T-cell immunoglobulin mucin-3 Drugs 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- 108010055044 Tetanus Toxin Proteins 0.000 description 1
- GLQFKOVWXPPFTP-VEVYYDQMSA-N Thr-Arg-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O GLQFKOVWXPPFTP-VEVYYDQMSA-N 0.000 description 1
- LHUBVKCLOVALIA-HJGDQZAQSA-N Thr-Arg-Gln Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O LHUBVKCLOVALIA-HJGDQZAQSA-N 0.000 description 1
- UNURFMVMXLENAZ-KJEVXHAQSA-N Thr-Arg-Tyr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O UNURFMVMXLENAZ-KJEVXHAQSA-N 0.000 description 1
- IRKWVRSEQFTGGV-VEVYYDQMSA-N Thr-Asn-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O IRKWVRSEQFTGGV-VEVYYDQMSA-N 0.000 description 1
- JXKMXEBNZCKSDY-JIOCBJNQSA-N Thr-Asp-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N)O JXKMXEBNZCKSDY-JIOCBJNQSA-N 0.000 description 1
- KWQBJOUOSNJDRR-XAVMHZPKSA-N Thr-Cys-Pro Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)N1CCC[C@@H]1C(=O)O)N)O KWQBJOUOSNJDRR-XAVMHZPKSA-N 0.000 description 1
- MMTOHPRBJKEZHT-BWBBJGPYSA-N Thr-Cys-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(O)=O MMTOHPRBJKEZHT-BWBBJGPYSA-N 0.000 description 1
- GUZGCDIZVGODML-NKIYYHGXSA-N Thr-Gln-His Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N)O GUZGCDIZVGODML-NKIYYHGXSA-N 0.000 description 1
- RKDFEMGVMMYYNG-WDCWCFNPSA-N Thr-Gln-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(O)=O RKDFEMGVMMYYNG-WDCWCFNPSA-N 0.000 description 1
- MQUZMZBFKCHVOB-HJGDQZAQSA-N Thr-Gln-Met Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCSC)C(O)=O MQUZMZBFKCHVOB-HJGDQZAQSA-N 0.000 description 1
- LGNBRHZANHMZHK-NUMRIWBASA-N Thr-Glu-Asp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)O)N)O LGNBRHZANHMZHK-NUMRIWBASA-N 0.000 description 1
- LHEZGZQRLDBSRR-WDCWCFNPSA-N Thr-Glu-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(O)=O LHEZGZQRLDBSRR-WDCWCFNPSA-N 0.000 description 1
- VULNJDORNLBPNG-SWRJLBSHSA-N Thr-Glu-Trp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N)O VULNJDORNLBPNG-SWRJLBSHSA-N 0.000 description 1
- MPUMPERGHHJGRP-WEDXCCLWSA-N Thr-Gly-Lys Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)O)N)O MPUMPERGHHJGRP-WEDXCCLWSA-N 0.000 description 1
- DJDSEDOKJTZBAR-ZDLURKLDSA-N Thr-Gly-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O DJDSEDOKJTZBAR-ZDLURKLDSA-N 0.000 description 1
- KBBRNEDOYWMIJP-KYNKHSRBSA-N Thr-Gly-Thr Chemical compound C[C@H]([C@@H](C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)O)N)O KBBRNEDOYWMIJP-KYNKHSRBSA-N 0.000 description 1
- JKGGPMOUIAAJAA-YEPSODPASA-N Thr-Gly-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](C(C)C)C(O)=O JKGGPMOUIAAJAA-YEPSODPASA-N 0.000 description 1
- YDWLCDQXLCILCZ-BWAGICSOSA-N Thr-His-Tyr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O YDWLCDQXLCILCZ-BWAGICSOSA-N 0.000 description 1
- YJCVECXVYHZOBK-KNZXXDILSA-N Thr-Ile-Pro Chemical compound CC[C@H](C)[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H]([C@@H](C)O)N YJCVECXVYHZOBK-KNZXXDILSA-N 0.000 description 1
- BVOVIGCHYNFJBZ-JXUBOQSCSA-N Thr-Leu-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(O)=O BVOVIGCHYNFJBZ-JXUBOQSCSA-N 0.000 description 1
- VTVVYQOXJCZVEB-WDCWCFNPSA-N Thr-Leu-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O VTVVYQOXJCZVEB-WDCWCFNPSA-N 0.000 description 1
- XIULAFZYEKSGAJ-IXOXFDKPSA-N Thr-Leu-His Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CNC=N1 XIULAFZYEKSGAJ-IXOXFDKPSA-N 0.000 description 1
- FLPZMPOZGYPBEN-PPCPHDFISA-N Thr-Leu-Ile Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O FLPZMPOZGYPBEN-PPCPHDFISA-N 0.000 description 1
- YOOAQCZYZHGUAZ-KATARQTJSA-N Thr-Leu-Ser Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YOOAQCZYZHGUAZ-KATARQTJSA-N 0.000 description 1
- WVVOFCVMHAXGLE-LFSVMHDDSA-N Thr-Phe-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(O)=O WVVOFCVMHAXGLE-LFSVMHDDSA-N 0.000 description 1
- PZSDPRBZINDEJV-HTUGSXCWSA-N Thr-Phe-Gln Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O PZSDPRBZINDEJV-HTUGSXCWSA-N 0.000 description 1
- WTMPKZWHRCMMMT-KZVJFYERSA-N Thr-Pro-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(O)=O WTMPKZWHRCMMMT-KZVJFYERSA-N 0.000 description 1
- KERCOYANYUPLHJ-XGEHTFHBSA-N Thr-Pro-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(O)=O KERCOYANYUPLHJ-XGEHTFHBSA-N 0.000 description 1
- GVMXJJAJLIEASL-ZJDVBMNYSA-N Thr-Pro-Thr Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)O)C(O)=O GVMXJJAJLIEASL-ZJDVBMNYSA-N 0.000 description 1
- SGAOHNPSEPVAFP-ZDLURKLDSA-N Thr-Ser-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)NCC(O)=O SGAOHNPSEPVAFP-ZDLURKLDSA-N 0.000 description 1
- RVMNUBQWPVOUKH-HEIBUPTGSA-N Thr-Ser-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O RVMNUBQWPVOUKH-HEIBUPTGSA-N 0.000 description 1
- IEZVHOULSUULHD-XGEHTFHBSA-N Thr-Ser-Val Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(O)=O IEZVHOULSUULHD-XGEHTFHBSA-N 0.000 description 1
- QYDKSNXSBXZPFK-ZJDVBMNYSA-N Thr-Thr-Arg Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O QYDKSNXSBXZPFK-ZJDVBMNYSA-N 0.000 description 1
- CSZFFQBUTMGHAH-UAXMHLISSA-N Thr-Thr-Trp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N)O CSZFFQBUTMGHAH-UAXMHLISSA-N 0.000 description 1
- CYCGARJWIQWPQM-YJRXYDGGSA-N Thr-Tyr-Ser Chemical compound C[C@@H](O)[C@H]([NH3+])C(=O)N[C@H](C(=O)N[C@@H](CO)C([O-])=O)CC1=CC=C(O)C=C1 CYCGARJWIQWPQM-YJRXYDGGSA-N 0.000 description 1
- OGOYMQWIWHGTGH-KZVJFYERSA-N Thr-Val-Ala Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O OGOYMQWIWHGTGH-KZVJFYERSA-N 0.000 description 1
- KPMIQCXJDVKWKO-IFFSRLJSSA-N Thr-Val-Glu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O KPMIQCXJDVKWKO-IFFSRLJSSA-N 0.000 description 1
- AKHDFZHUPGVFEJ-YEPSODPASA-N Thr-Val-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O AKHDFZHUPGVFEJ-YEPSODPASA-N 0.000 description 1
- MNYNCKZAEIAONY-XGEHTFHBSA-N Thr-Val-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O MNYNCKZAEIAONY-XGEHTFHBSA-N 0.000 description 1
- KZTLZZQTJMCGIP-ZJDVBMNYSA-N Thr-Val-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KZTLZZQTJMCGIP-ZJDVBMNYSA-N 0.000 description 1
- 239000000365 Topoisomerase I Inhibitor Substances 0.000 description 1
- 239000000317 Topoisomerase II Inhibitor Substances 0.000 description 1
- WFZYXGSAPWKTHR-XEGUGMAKSA-N Trp-Ala-Gln Chemical compound C[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N WFZYXGSAPWKTHR-XEGUGMAKSA-N 0.000 description 1
- NMCBVGFGWSIGSB-NUTKFTJISA-N Trp-Ala-Leu Chemical compound C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N NMCBVGFGWSIGSB-NUTKFTJISA-N 0.000 description 1
- IQGJAHMZWBTRIF-UBHSHLNASA-N Trp-Asp-Asn Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)N)C(=O)O)N IQGJAHMZWBTRIF-UBHSHLNASA-N 0.000 description 1
- KVMZNMYZCKORIG-UBHSHLNASA-N Trp-Cys-Asp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)O)N KVMZNMYZCKORIG-UBHSHLNASA-N 0.000 description 1
- WMBFONUKQXGLMU-WDSOQIARSA-N Trp-Leu-Val Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N WMBFONUKQXGLMU-WDSOQIARSA-N 0.000 description 1
- GEGYPBOPIGNZIF-CWRNSKLLSA-N Trp-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)N)C(=O)O GEGYPBOPIGNZIF-CWRNSKLLSA-N 0.000 description 1
- GSCPHMSPGQSZJT-JYBASQMISA-N Trp-Ser-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N)O GSCPHMSPGQSZJT-JYBASQMISA-N 0.000 description 1
- DDHFMBDACJYSKW-AQZXSJQPSA-N Trp-Thr-Asp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)N)O DDHFMBDACJYSKW-AQZXSJQPSA-N 0.000 description 1
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
- IIJWXEUNETVJPV-IHRRRGAJSA-N Tyr-Arg-Ser Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CO)C(=O)O)N)O IIJWXEUNETVJPV-IHRRRGAJSA-N 0.000 description 1
- DANHCMVVXDXOHN-SRVKXCTJSA-N Tyr-Asp-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 DANHCMVVXDXOHN-SRVKXCTJSA-N 0.000 description 1
- MPKPIWFFDWVJGC-IRIUXVKKSA-N Tyr-Gln-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC1=CC=C(C=C1)O)N)O MPKPIWFFDWVJGC-IRIUXVKKSA-N 0.000 description 1
- LOOCQRRBKZTPKO-AVGNSLFASA-N Tyr-Glu-Asn Chemical compound NC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 LOOCQRRBKZTPKO-AVGNSLFASA-N 0.000 description 1
- SLCSPPCQWUHPPO-JYJNAYRXSA-N Tyr-Glu-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 SLCSPPCQWUHPPO-JYJNAYRXSA-N 0.000 description 1
- GIOBXJSONRQHKQ-RYUDHWBXSA-N Tyr-Gly-Glu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(O)=O GIOBXJSONRQHKQ-RYUDHWBXSA-N 0.000 description 1
- AZGZDDNKFFUDEH-QWRGUYRKSA-N Tyr-Gly-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CC1=CC=C(O)C=C1 AZGZDDNKFFUDEH-QWRGUYRKSA-N 0.000 description 1
- CVXURBLRELTJKO-BWAGICSOSA-N Tyr-His-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CC2=CC=C(C=C2)O)N)O CVXURBLRELTJKO-BWAGICSOSA-N 0.000 description 1
- SFSZDJHNAICYSD-PMVMPFDFSA-N Tyr-His-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CC3=CN=CN3)NC(=O)[C@H](CC4=CC=C(C=C4)O)N SFSZDJHNAICYSD-PMVMPFDFSA-N 0.000 description 1
- HVPPEXXUDXAPOM-MGHWNKPDSA-N Tyr-Ile-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 HVPPEXXUDXAPOM-MGHWNKPDSA-N 0.000 description 1
- HFJJDMOFTCQGEI-STECZYCISA-N Tyr-Ile-Met Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N HFJJDMOFTCQGEI-STECZYCISA-N 0.000 description 1
- DWAMXBFJNZIHMC-KBPBESRZSA-N Tyr-Leu-Gly Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O DWAMXBFJNZIHMC-KBPBESRZSA-N 0.000 description 1
- ZMKDQRJLMRZHRI-ACRUOGEOSA-N Tyr-Phe-His Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC2=CN=CN2)C(=O)O)NC(=O)[C@H](CC3=CC=C(C=C3)O)N ZMKDQRJLMRZHRI-ACRUOGEOSA-N 0.000 description 1
- WURLIFOWSMBUAR-SLFFLAALSA-N Tyr-Phe-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC3=CC=C(C=C3)O)N)C(=O)O WURLIFOWSMBUAR-SLFFLAALSA-N 0.000 description 1
- FGVFBDZSGQTYQX-UFYCRDLUSA-N Tyr-Phe-Val Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O FGVFBDZSGQTYQX-UFYCRDLUSA-N 0.000 description 1
- AUZADXNWQMBZOO-JYJNAYRXSA-N Tyr-Pro-Arg Chemical compound C([C@H](N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)C1=CC=C(O)C=C1 AUZADXNWQMBZOO-JYJNAYRXSA-N 0.000 description 1
- XJPXTYLVMUZGNW-IHRRRGAJSA-N Tyr-Pro-Asp Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O XJPXTYLVMUZGNW-IHRRRGAJSA-N 0.000 description 1
- SOEGLGLDSUHWTI-STECZYCISA-N Tyr-Pro-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CC1=CC=C(O)C=C1 SOEGLGLDSUHWTI-STECZYCISA-N 0.000 description 1
- UMSZZGTXGKHTFJ-SRVKXCTJSA-N Tyr-Ser-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 UMSZZGTXGKHTFJ-SRVKXCTJSA-N 0.000 description 1
- BYOHPUZJVXWHAE-BYULHYEWSA-N Val-Asn-Asn Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(=O)N)C(=O)O)N BYOHPUZJVXWHAE-BYULHYEWSA-N 0.000 description 1
- OGNMURQZFMHFFD-NHCYSSNCSA-N Val-Asn-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O)N OGNMURQZFMHFFD-NHCYSSNCSA-N 0.000 description 1
- IDKGBVZGNTYYCC-QXEWZRGKSA-N Val-Asn-Pro Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(O)=O IDKGBVZGNTYYCC-QXEWZRGKSA-N 0.000 description 1
- VLOYGOZDPGYWFO-LAEOZQHASA-N Val-Asp-Glu Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O VLOYGOZDPGYWFO-LAEOZQHASA-N 0.000 description 1
- ZQGPWORGSNRQLN-NHCYSSNCSA-N Val-Asp-His Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N ZQGPWORGSNRQLN-NHCYSSNCSA-N 0.000 description 1
- DDNIHOWRDOXXPF-NGZCFLSTSA-N Val-Asp-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N1CCC[C@@H]1C(=O)O)N DDNIHOWRDOXXPF-NGZCFLSTSA-N 0.000 description 1
- XEYUMGGWQCIWAR-XVKPBYJWSA-N Val-Gln-Gly Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)NCC(=O)O)N XEYUMGGWQCIWAR-XVKPBYJWSA-N 0.000 description 1
- PGBJAZDAEWPDAA-NHCYSSNCSA-N Val-Gln-Met Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCSC)C(=O)O)N PGBJAZDAEWPDAA-NHCYSSNCSA-N 0.000 description 1
- UZDHNIJRRTUKKC-DLOVCJGASA-N Val-Gln-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](C(C)C)C(=O)O)N UZDHNIJRRTUKKC-DLOVCJGASA-N 0.000 description 1
- VLDMQVZZWDOKQF-AUTRQRHGSA-N Val-Glu-Gln Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)N)C(=O)O)N VLDMQVZZWDOKQF-AUTRQRHGSA-N 0.000 description 1
- VVZDBPBZHLQPPB-XVKPBYJWSA-N Val-Glu-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O VVZDBPBZHLQPPB-XVKPBYJWSA-N 0.000 description 1
- ZXAGTABZUOMUDO-GVXVVHGQSA-N Val-Glu-Lys Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)O)N ZXAGTABZUOMUDO-GVXVVHGQSA-N 0.000 description 1
- DJEVQCWNMQOABE-RCOVLWMOSA-N Val-Gly-Asp Chemical compound CC(C)[C@@H](C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)O)N DJEVQCWNMQOABE-RCOVLWMOSA-N 0.000 description 1
- YTPLVNUZZOBFFC-SCZZXKLOSA-N Val-Gly-Pro Chemical compound CC(C)[C@H](N)C(=O)NCC(=O)N1CCC[C@@H]1C(O)=O YTPLVNUZZOBFFC-SCZZXKLOSA-N 0.000 description 1
- XBRMBDFYOFARST-AVGNSLFASA-N Val-His-Val Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@@H](C(C)C)C(=O)O)N XBRMBDFYOFARST-AVGNSLFASA-N 0.000 description 1
- APEBUJBRGCMMHP-HJWJTTGWSA-N Val-Ile-Phe Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 APEBUJBRGCMMHP-HJWJTTGWSA-N 0.000 description 1
- BZWUSZGQOILYEU-STECZYCISA-N Val-Ile-Tyr Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 BZWUSZGQOILYEU-STECZYCISA-N 0.000 description 1
- FEXILLGKGGTLRI-NHCYSSNCSA-N Val-Leu-Asn Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)O)NC(=O)[C@H](C(C)C)N FEXILLGKGGTLRI-NHCYSSNCSA-N 0.000 description 1
- LYERIXUFCYVFFX-GVXVVHGQSA-N Val-Leu-Glu Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](C(C)C)N LYERIXUFCYVFFX-GVXVVHGQSA-N 0.000 description 1
- ZHQWPWQNVRCXAX-XQQFMLRXSA-N Val-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](C(C)C)N ZHQWPWQNVRCXAX-XQQFMLRXSA-N 0.000 description 1
- SYSWVVCYSXBVJG-RHYQMDGZSA-N Val-Leu-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)N)O SYSWVVCYSXBVJG-RHYQMDGZSA-N 0.000 description 1
- DIOSYUIWOQCXNR-ONGXEEELSA-N Val-Lys-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O DIOSYUIWOQCXNR-ONGXEEELSA-N 0.000 description 1
- SVFRYKBZHUGKLP-QXEWZRGKSA-N Val-Met-Asn Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(=O)N)C(=O)O)N SVFRYKBZHUGKLP-QXEWZRGKSA-N 0.000 description 1
- ILMVQSHENUZYIZ-JYJNAYRXSA-N Val-Met-Tyr Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=C(C=C1)O)C(=O)O)N ILMVQSHENUZYIZ-JYJNAYRXSA-N 0.000 description 1
- DEGUERSKQBRZMZ-FXQIFTODSA-N Val-Ser-Ala Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O DEGUERSKQBRZMZ-FXQIFTODSA-N 0.000 description 1
- AJNUKMZFHXUBMK-GUBZILKMSA-N Val-Ser-Arg Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N AJNUKMZFHXUBMK-GUBZILKMSA-N 0.000 description 1
- UGFMVXRXULGLNO-XPUUQOCRSA-N Val-Ser-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O UGFMVXRXULGLNO-XPUUQOCRSA-N 0.000 description 1
- MNSSBIHFEUUXNW-RCWTZXSCSA-N Val-Thr-Arg Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N MNSSBIHFEUUXNW-RCWTZXSCSA-N 0.000 description 1
- DLRZGNXCXUGIDG-KKHAAJSZSA-N Val-Thr-Asp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](C(C)C)N)O DLRZGNXCXUGIDG-KKHAAJSZSA-N 0.000 description 1
- BZDGLJPROOOUOZ-XGEHTFHBSA-N Val-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](C(C)C)N)O BZDGLJPROOOUOZ-XGEHTFHBSA-N 0.000 description 1
- UVHFONIHVHLDDQ-IFFSRLJSSA-N Val-Thr-Glu Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](C(C)C)N)O UVHFONIHVHLDDQ-IFFSRLJSSA-N 0.000 description 1
- XNLUVJPMPAZHCY-JYJNAYRXSA-N Val-Val-Phe Chemical compound CC(C)[C@H]([NH3+])C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C([O-])=O)CC1=CC=CC=C1 XNLUVJPMPAZHCY-JYJNAYRXSA-N 0.000 description 1
- LLJLBRRXKZTTRD-GUBZILKMSA-N Val-Val-Ser Chemical compound CC(C)[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)O)N LLJLBRRXKZTTRD-GUBZILKMSA-N 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 108010081404 acein-2 Proteins 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000011226 adjuvant chemotherapy Methods 0.000 description 1
- 108010076324 alanyl-glycyl-glycine Proteins 0.000 description 1
- 108010086434 alanyl-seryl-glycine Proteins 0.000 description 1
- 108010045350 alanyl-tyrosyl-alanine Proteins 0.000 description 1
- 108010044940 alanylglutamine Proteins 0.000 description 1
- 108010070944 alanylhistidine Proteins 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000001745 anti-biotin effect Effects 0.000 description 1
- 230000006023 anti-tumor response Effects 0.000 description 1
- 102000025171 antigen binding proteins Human genes 0.000 description 1
- 108091000831 antigen binding proteins Proteins 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 239000003080 antimitotic agent Substances 0.000 description 1
- 108010013835 arginine glutamate Proteins 0.000 description 1
- 108010006195 arginyl-glycyl-aspartyl-cysteine Proteins 0.000 description 1
- 108010069926 arginyl-glycyl-serine Proteins 0.000 description 1
- 229910052785 arsenic Inorganic materials 0.000 description 1
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 description 1
- 239000010425 asbestos Substances 0.000 description 1
- 108010010430 asparagine-proline-alanine Proteins 0.000 description 1
- 108010038633 aspartylglutamate Proteins 0.000 description 1
- 108010047857 aspartylglycine Proteins 0.000 description 1
- 108010068265 aspartyltyrosine Proteins 0.000 description 1
- 230000006472 autoimmune response Effects 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 125000006355 carbonyl methylene group Chemical group [H]C([H])([*:2])C([*:1])=O 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 230000008045 co-localization Effects 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000004154 complement system Effects 0.000 description 1
- 238000002591 computed tomography Methods 0.000 description 1
- 239000000562 conjugate Substances 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- ZOOGRGPOEVQQDX-KHLHZJAASA-N cyclic guanosine monophosphate Chemical compound C([C@H]1O2)O[P@](O)(=O)O[C@@H]1[C@H](O)[C@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-KHLHZJAASA-N 0.000 description 1
- 108010060199 cysteinylproline Proteins 0.000 description 1
- 108010069495 cysteinyltyrosine Proteins 0.000 description 1
- 210000005220 cytoplasmic tail Anatomy 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- FSXRLASFHBWESK-UHFFFAOYSA-N dipeptide phenylalanyl-tyrosine Natural products C=1C=C(O)C=CC=1CC(C(O)=O)NC(=O)C(N)CC1=CC=CC=C1 FSXRLASFHBWESK-UHFFFAOYSA-N 0.000 description 1
- 206010013023 diphtheria Diseases 0.000 description 1
- 229960003983 diphtheria toxoid Drugs 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 230000004720 fertilization Effects 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 108010017007 glucose-regulated proteins Proteins 0.000 description 1
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 1
- 108010008237 glutamyl-valyl-glycine Proteins 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 229930004094 glycosylphosphatidylinositol Natural products 0.000 description 1
- HPAIKDPJURGQLN-UHFFFAOYSA-N glycyl-L-histidyl-L-phenylalanine Natural products C=1C=CC=CC=1CC(C(O)=O)NC(=O)C(NC(=O)CN)CC1=CN=CN1 HPAIKDPJURGQLN-UHFFFAOYSA-N 0.000 description 1
- XBGGUPMXALFZOT-UHFFFAOYSA-N glycyl-L-tyrosine hemihydrate Natural products NCC(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 XBGGUPMXALFZOT-UHFFFAOYSA-N 0.000 description 1
- 108010023364 glycyl-histidyl-arginine Proteins 0.000 description 1
- 108010028188 glycyl-histidyl-serine Proteins 0.000 description 1
- 108010010147 glycylglutamine Proteins 0.000 description 1
- 108010020688 glycylhistidine Proteins 0.000 description 1
- 108010015792 glycyllysine Proteins 0.000 description 1
- 108010077515 glycylproline Proteins 0.000 description 1
- 108010036413 histidylglycine Proteins 0.000 description 1
- 108010085325 histidylproline Proteins 0.000 description 1
- 238000007489 histopathology method Methods 0.000 description 1
- 230000008348 humoral response Effects 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000126 in silico method Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 230000007154 intracellular accumulation Effects 0.000 description 1
- 230000005865 ionizing radiation Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 108010078274 isoleucylvaline Proteins 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 210000001821 langerhans cell Anatomy 0.000 description 1
- 208000003849 large cell carcinoma Diseases 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 108010044056 leucyl-phenylalanine Proteins 0.000 description 1
- 108010000761 leucylarginine Proteins 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 201000005243 lung squamous cell carcinoma Diseases 0.000 description 1
- 208000037841 lung tumor Diseases 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 108010009298 lysylglutamic acid Proteins 0.000 description 1
- 108010064235 lysylglycine Proteins 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 108010005942 methionylglycine Proteins 0.000 description 1
- 108010068488 methionylphenylalanine Proteins 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 238000002493 microarray Methods 0.000 description 1
- JMUHBNWAORSSBD-WKYWBUFDSA-N mifamurtide Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCCCCCCCCCC)COP(O)(=O)OCCNC(=O)[C@H](C)NC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](C)O[C@H]1[C@H](O)[C@@H](CO)OC(O)[C@@H]1NC(C)=O JMUHBNWAORSSBD-WKYWBUFDSA-N 0.000 description 1
- 229960005225 mifamurtide Drugs 0.000 description 1
- 108700007621 mifamurtide Proteins 0.000 description 1
- 231100000324 minimal toxicity Toxicity 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- NKAAEMMYHLFEFN-UHFFFAOYSA-M monosodium tartrate Chemical compound [Na+].OC(=O)C(O)C(O)C([O-])=O NKAAEMMYHLFEFN-UHFFFAOYSA-M 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 230000007498 myristoylation Effects 0.000 description 1
- 210000004898 n-terminal fragment Anatomy 0.000 description 1
- 238000011227 neoadjuvant chemotherapy Methods 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229960003301 nivolumab Drugs 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 229940023146 nucleic acid vaccine Drugs 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 208000005963 oophoritis Diseases 0.000 description 1
- 230000000242 pagocytic effect Effects 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000013618 particulate matter Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 108010024607 phenylalanylalanine Proteins 0.000 description 1
- 108010018625 phenylalanylarginine Proteins 0.000 description 1
- 108010073101 phenylalanylleucine Proteins 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 210000004224 pleura Anatomy 0.000 description 1
- 108700002563 poly ICLC Proteins 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
- 230000013823 prenylation Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 108010025826 prolyl-leucyl-arginine Proteins 0.000 description 1
- 108010077112 prolyl-proline Proteins 0.000 description 1
- 108010079317 prolyl-tyrosine Proteins 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000011363 radioimmunotherapy Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 229910052895 riebeckite Inorganic materials 0.000 description 1
- 238000010079 rubber tapping Methods 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 108010048818 seryl-histidine Proteins 0.000 description 1
- 230000037432 silent mutation Effects 0.000 description 1
- 238000002603 single-photon emission computed tomography Methods 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000012192 staining solution Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 229940118376 tetanus toxin Drugs 0.000 description 1
- 229960000814 tetanus toxoid Drugs 0.000 description 1
- HODRFAVLXIFVTR-RKDXNWHRSA-N tevenel Chemical compound NS(=O)(=O)C1=CC=C([C@@H](O)[C@@H](CO)NC(=O)C(Cl)Cl)C=C1 HODRFAVLXIFVTR-RKDXNWHRSA-N 0.000 description 1
- 210000000779 thoracic wall Anatomy 0.000 description 1
- 108010072986 threonyl-seryl-lysine Proteins 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- AVWQQPYHYQKEIZ-UHFFFAOYSA-K trisodium;2-dodecylbenzenesulfonate;3-dodecylbenzenesulfonate;4-dodecylbenzenesulfonate Chemical compound [Na+].[Na+].[Na+].CCCCCCCCCCCCC1=CC=C(S([O-])(=O)=O)C=C1.CCCCCCCCCCCCC1=CC=CC(S([O-])(=O)=O)=C1.CCCCCCCCCCCCC1=CC=CC=C1S([O-])(=O)=O AVWQQPYHYQKEIZ-UHFFFAOYSA-K 0.000 description 1
- 108010029384 tryptophyl-histidine Proteins 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 108010051110 tyrosyl-lysine Proteins 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- IBIDRSSEHFLGSD-UHFFFAOYSA-N valinyl-arginine Natural products CC(C)C(N)C(=O)NC(C(O)=O)CCCN=C(N)N IBIDRSSEHFLGSD-UHFFFAOYSA-N 0.000 description 1
- 108010009962 valyltyrosine Proteins 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001102—Receptors, cell surface antigens or cell surface determinants
- A61K39/001111—Immunoglobulin superfamily
- A61K39/001114—CD74, Ii, MHC class II invariant chain or MHC class II gamma chain
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/15—Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
- A61K38/1774—Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001102—Receptors, cell surface antigens or cell surface determinants
- A61K39/001111—Immunoglobulin superfamily
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5154—Antigen presenting cells [APCs], e.g. dendritic cells or macrophages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5158—Antigen-pulsed cells, e.g. T-cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/53—DNA (RNA) vaccination
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Cell Biology (AREA)
- Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Oncology (AREA)
- Zoology (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Developmental Biology & Embryology (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Virology (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Optics & Photonics (AREA)
- Endocrinology (AREA)
Abstract
本发明涉及肺癌及其转移的治疗和诊断。更具体地,本发明涉及提供免疫原性多肽的抗原来源的此类治疗用途,所述免疫原性多肽包含癌细胞相关蛋白的免疫原性部分,所述癌细胞相关蛋白优选为透明带(ZP)蛋白,尤其是ZP3蛋白或其细胞外结构域,由此所述抗原来源诱导针对肺癌细胞的细胞免疫应答。抗原来源可以是包含此类免疫原性ZP多肽的蛋白质组合物,编码免疫原性ZP多肽的核酸,或者表达或呈递免疫原性ZP多肽的细胞。另外,本发明涉及包含T细胞受体的T细胞的治疗用途,所述T细胞受体结合MHC‑肽复合物,其中所述肽是来自免疫原性ZP多肽的肽。本发明进一步涉及与免疫原性ZP多肽特异性结合的抗体的治疗和/或诊断用途。
Description
技术领域
本发明涉及肺癌及其转移的治疗和诊断。更具体地,本发明涉及提供癌细胞相关蛋白的至少免疫原性部分的抗原来源,所述癌细胞相关蛋白优选为透明带(ZP)蛋白,尤其是ZP3蛋白。此类抗原来源可以用于疫苗和药物组合物中,用于原发性和/或复发性肺癌及其转移的治疗性和预防性治疗。
背景技术
肺癌指源于肺组织的癌症,尽管绝大多数(大约90%-95%)的肺癌是起于上皮细胞的癌-恶性肿瘤,但它可以起于肺的任何部分。存在两种主要类型的肺癌,其通过组织病理学分析分类为:非小细胞肺癌(80.4%)和小细胞肺癌(16.8%)。癌症也可以起于胸膜(称为间皮瘤),或罕见地起于肺内的支持组织例如血管。任何癌症的主要原因包括非遗传因素,例如暴露于致癌物(例如烟草烟雾、石棉、砷、颗粒物质)、电离辐射和病毒感染。流行病学研究已显示,遗传因素可能引起发展肺癌的风险。
肺癌是最常见的癌症之一。在2007年,肺癌占所有癌症诊断的大约15%以及所有癌症死亡的28%。它是男性和女性中第四大被诊断的癌症,但它每年都是男性和女性两者中死于癌症的第一大原因。大多数肺癌病例在晚期阶段时被诊断,赋予较差的预后。肺癌是高度致命的,在美国,其5年患者生存率仅为14%。用于肺癌的治疗取决于癌症的特定细胞类型、转移以及患者的体力状况。常见的治疗包括手术的(组合)、化学疗法(例如顺铂、卡铂、吉西他滨、紫杉醇、多西他赛、依托泊苷、长春瑞滨、托泊替康、伊立替康)、放射疗法、免疫疗法(例如阿特珠单抗、纳武单抗、帕博利珠单抗)和‘靶向疗法’(例如吉非替尼、厄洛替尼、贝伐珠单抗)。许多‘靶向试剂’处于临床开发的早期阶段,例如环加氧酶2抑制剂、细胞凋亡促进剂依昔舒林、蛋白酶体抑制剂、贝沙罗汀和表皮生长因子受体抑制剂西妥昔单抗。
小细胞肺癌主要用放射和使用顺铂或依托泊苷的化学疗法进行治疗,有时与卡铂、吉西他滨、紫杉醇、长春瑞滨、托泊替康或伊立替康组合。手术对小细胞肺癌中的存活没有可证实的影响。在广泛阶段的小细胞肺癌中,塞来昔布可以与依托泊苷组合用于改善的结果。
非小细胞肺癌(NSCLC)是除小细胞肺癌(SCLC)外的任何类型的上皮肺癌。NSCLC占所有肺癌的约85%。作为一个类别,与SCLC相比,NSCLC对化学疗法相对不敏感。尽管化学疗法越来越多地在手术前(新辅助化学疗法)和手术后(辅助化学疗法)均使用,但在可能时,它们主要通过具有治愈意图的手术切除进行治疗。目前,NSCLC的第一线治疗涉及手术和使用顺铂或卡铂的化学疗法,经常与吉西他滨、紫杉醇、多西他赛、依托泊苷或长春瑞滨组合。手术是限于一个肺,直到IIIA期的NSCLC中的唯一选项。如果手术不再是选项,则给予初始化学疗法。
尽管现有的疗法在肺癌的管理中提供了一些益处,但前景仍然普遍不佳,并且找到更有效和毒性更小的治疗模式仍然绝对必要。鉴定用于肺癌治疗的新型治疗靶是实现这个目标的关键步骤。
分子医学中的进步已增加了肿瘤特异性抗原中的兴趣,所述肿瘤特异性抗原可以充当关于各种免疫治疗学或小分子策略的靶。
为了充当关于免疫治疗癌症策略的合适靶,此类抗原应该是在癌症组织中高度表达的,并且理想地不在正常组织中高度表达。然而,在对于生命并非必要的组织中的表达可以是可接受的。
以前在本领域中已描述了通过主动免疫来治疗ZP表达肿瘤的概念。例如,Rahman等人(A novel treatment strategy for ovarian cancer based on immunization withzona pellucida protein(ZP)3.FASEB J.2012Jan;26(1):324-33),证明了通过分别诱发针对ZP3蛋白和ZP3表达细胞的体液和细胞疫苗接种,来治疗转基因小鼠中的恶性卵巢肿瘤的原理。此外,作为用于绝育的方法,用ZP蛋白的主动免疫是在大型野生动物中的常见实践,这证实了其可行性和安全性(参见例如Gupta和Minhas,Frontiers In Bioscience,2017,Scholar,9,357-374,http://www.bioscience.org/2017/v9s/af/492/2.htm;Mask等人,2015,Theriogenology;84(2):261-267)。进行了众多研究,其中生育力中的减少与抗体滴度相关(Shresta等人,2015,Vaccine 33,133-140;Harris等人,1999,Protein ExprPurif;16(2):298-307;Martinez和Harris,2000,J Reprod Fertil.;120(1):19-32)。特别地对于用重组ZP3和ZP4的免疫描述了另外的退行性卵巢病理学(例如Govind等人,2002,Vaccine 21,78-88;Paterson等人,1998,Am J Reprod Immunol 40,198-209;以及Srivastava等人,2002,Reproduction 123,847-857)。在卵巢自身免疫性疾病的研究中,研究人员证实,可以通过用含有MHC II类结合表位的15氨基酸的ZP3多肽的疫苗接种,诱发ZP3特异性CD4+T细胞应答,在小鼠中诱导***(卵巢组织损伤)(Rhim等人,1992,J.Clin.Invest.89,28-35)。然而,尚未报道ZP蛋白在肺癌中的表达。
本发明的目的是提供用于治疗和/或复发性肺癌及其转移的新型免疫治疗策略。
发明内容
本发明人已惊讶地发现,透明带(ZP)蛋白,尤其是透明带3蛋白(ZP3)在肺癌细胞中表达,并且构成用于治疗肺癌及其转移、以及其诊断的免疫治疗策略的合适靶。
ZP3通常在女性中的所谓的‘透明带’中发现,所述透明带形成围绕***的细胞外基质。这个透明带诱导对***的顶体反应,确定关于受精的物种特异性,并且预防哺乳动物中的多精受精。透明带含有四种主要的糖蛋白,ZP1、ZP2、ZP3和ZP4。为了方便起见,我们在本文中将指透明带或ZP“蛋白质”,除非另有特别说明,否则该术语应理解为包括透明带蛋白的糖基化形式和非糖基化形式两者。
本发明在于以下发现:肺癌细胞可以展示ZP蛋白的显著表达,达到可以应用免疫治疗策略的程度,例如被动免疫、主动免疫和使用免疫缀合物的靶向疗法,以导致以下中的至少一种:i)减少原发性肿瘤的生长或大小,ii)减少源于其的转移灶的生长或大小,iii)根除肿瘤,和iv)增加存活。
本策略同样适合于预防肺癌的转移,以及预防先前治疗的对象中肺癌的复发。因此,应理解,术语“肺癌细胞”和“表达ZP的肺癌细胞”还包括衍生自肺癌细胞的此类细胞,因为它们可能出现在除肺以外的身体其它部分中,例如由于转移。
本文的实施例4描述了在具有表达hZP3的肿瘤的人源化HLA-A2转基因小鼠中的临床前研究。这些转基因小鼠用hZP3多肽(aa 1-383)和hZP3 HLA-A2限制性T细胞表位的疫苗接种诱导CD8+T细胞。此外,未观察到肿瘤大小中的增加,而肿瘤大小在用PBS处理的对照小鼠中增加。
以前从未确定过ZP蛋白在肺癌细胞中的表达。因此,在现有技术中不存在肺癌细胞事实上可以通过基于ZP的免疫疗法进行靶向的指示。因此,本发明首次提供了靶向作为肿瘤特异性抗原的ZP蛋白,来治疗对象中的肺癌的方法。如本领域技术人员基于本公开内容将理解的,此类疗法包括被动免疫、主动免疫以及使用免疫缀合物的靶向疗法。
下文将更详细地描述本发明的这些和其它方面。
具体实施方式
本发明的第一个方面涉及用于在有此需要的对象中的原发性和/或复发性肺癌及其转移的治疗性和/或预防性治疗或诊断的方法,其中所述方法包括向所述对象施用以下中的至少一种:
·能够诱发针对人透明带蛋白(hZP),优选hZP3或hZP3(23-350)的细胞或体液免疫应答的免疫原性多肽的来源;
·包含结合MHC-肽复合物的T细胞受体的T细胞,其中所述肽是来自hZP,优选hZP3或hZP3(23-350)的肽;
·与hZP,优选hZP3或hZP3(23-350)特异性结合的抗体或其片段;和
·包含编码所述多肽或抗体的核酸序列的遗传构建体,其中所述遗传构建体被配置为在人中递送且表达。
如本文使用的,术语‘肺癌’指原发性和/或复发性肺癌以及其可能已在体内任何地方安定的转移灶。优选地,本方法是用于治疗源于上皮细胞的癌症的方法,所述癌症也统称为癌。更特别地,本发明涉及NSCLC以及其转移的治疗,所述NSCLC包括腺癌、鳞状细胞癌和大细胞癌。
通常,出于本发明的目的,术语‘肺癌’指恶性疾病或状况,并且可以与某些其它术语如‘(恶性)肺肿瘤’和‘(恶性)肿瘤性疾病’互换使用。通常,出于本发明的目的,术语‘肺癌’并不涵盖良性赘生物和/或良性肿瘤。然而,在其最广泛的意义上,本发明还可以涵盖患有此类良性状况的对象的治疗,以预防其进展成或发展为恶性肿瘤(肺癌)。肺癌可以通过使用美国癌症TNM联合委员会(American Joint Committee on Cancer TNM)(肿瘤、***、转移灶)分类法如下进行分期:
·I期:肿瘤仅在一个肺中发现,并且尚未扩散到任何***。
·II期:肿瘤已扩散到周围肺内包含的***。
·IIIa期:肿瘤已扩散到肺以外的***,扩散到气管区域的***,包括与癌症起始的同一侧上的胸壁和横膈膜。
·IIIb期:肿瘤已扩散到相对肺上或颈中的***。
·IV期:肿瘤已扩散到肺的其它部分或远处扩散到全身。
上述TNM分期***不常用于SCLC患者,因为大多数病例在诊断时具有怀疑或明确的转移性疾病。这些患者中的存活通常不受肿瘤累及程度中的微小差异的影响。相反,大多数专家使用由美国退伍军人肺癌协会(Veterans Administration Lung Cancer StudyGroup)创建的简单的两阶段***。这个***将SCLC定义为“有限”或“广泛”阶段。本方法在所有阶段都产生显著的应答率,并且因此,在其最广泛的意义上,本发明涉及上述阶段中的任何一个的肺癌治疗。
根据本发明的方法可以构成主要治疗方法,或者在使用任何其它治疗方法治疗患者之前、之中或之后作为辅助疗法应用,所述任何其它治疗方法包括例如:
·手术;
·放射疗法;
·化学疗法,例如使用基于铂的药物,例如顺铂和卡铂;核苷类似物,例如吉西他滨,紫杉烷例如紫杉醇和多西他赛;拓扑异构酶I抑制剂,例如拓泊替康和伊立替康;拓扑异构酶II抑制剂,例如依托泊苷;以及抗有丝***药物,例如长春瑞滨;
·‘靶向疗法’,例如使用EGFR抑制剂,例如吉非替尼;酪氨酸激酶抑制剂,例如厄洛替尼;VEGF-A抑制剂,例如贝伐珠单抗;环加氧酶2抑制剂;环磷酸鸟苷磷酸二酯酶的抑制剂,例如依昔舒林;蛋白酶体抑制剂;RXR激动剂,例如贝沙罗汀;以及EGFR抑制剂,例如西妥昔单抗;
·免疫调节疗法,例如如下所述;和
·其组合。
本发明的方法优选与免疫调节疗法组合。当本发明的方法包括施用能够诱发针对hZP的细胞或体液免疫应答的免疫原性多肽的来源时,此类方法与免疫调节疗法组合是特别优选的。可以与本发明的方法组合的免疫调节疗法可以选自以下中的一种或多种:
·使用检查点抑制剂,例如针对PD1、PDL1、CTLA4、TIM-3和/或LAG-3的抗体;
·使用靶向所选TNF受体家族成员的抗体,例如针对CD40、4-1BB、CD137、OX-40/CD134和/或CD27的抗体;
·使用免疫抑制性细胞因子,例如IL-10、TGF-β和/或IL-6;
·使用γC细胞因子,例如IL-7、IL-15和IL-21和/r IL-2,因为这些细胞因子具有扩增经历抗原的T细胞的能力;
·使用例如由Kaczanowska等人(J Leukoc Biol.2013Jun;93(6):847–863)描述的TLR激动剂,和/或如下文所述的TLR配体;
·使用恒定自然杀伤T(iNKT)细胞的激动剂,例如由Cerundolo等人(Curr OpinImmunol.2010;22(3):417-24)描述的合成iNKT激动剂。
本发明提供了适合用于治疗原发性肺癌、复发性肺癌及其转移的方法,其在本文中被视为构成‘治疗性治疗’或‘治愈性治疗’,以及用于预防肺癌的转移和/或复发的方法,任选地在其它治疗方法(例如之前所述的)之后或与其它治疗方法组合,其在本文中被视为构成‘预防性治疗’。
对于本发明的方法,待治疗的对象优选是人,并且可以是男性或女性。当待治疗的对象是(绝经前)女性时,可以通过监测针对卵巢组织的自身免疫来监测该方法的临床功效。例如,血液激素水平然后可以用作关于临床功效的生物标记物,并且取代临床终点(PFS、OS),以缩短读出时间线。
本发明基于ZP蛋白由癌细胞表达的发现,其对于免疫治疗策略呈现了各种选项。然而,由于不同的肿瘤可能具有不同的或改变的基因表达模式,因此也可能出现未表达ZP蛋白至任何显著程度的某些肺癌,如技术人员将理解的。因此,通常,本发明涉及表达ZP蛋白,优选ZP3的肺癌或其转移的治疗。
多年来,ZP糖蛋白组分的命名一直相当不一致,采用了几个标准,包括表观分子量、蛋白质序列长度和序列同一性比较,其已导致混淆的命名法。Harris等人[(1994)DNAseq.96:829-834]提议了统一的命名***,其中ZP基因按其编码的蛋白质序列的长度从最长到最短的次序命名。由于在这些标准下,小鼠ZP基因的次序依次为ZP2、ZP1和ZP3,因此引入了新***,其中ZP2变为ZPA,ZP1变为ZPB,ZP3变为ZPC。最近以来,Hughes等人[(1999)BBA-Gene Structure and Expression 1447:303-306],尤其报道了已知小鼠ZP1基因的真正的人直系同源物不是ZPB,而是存在独特的人ZP1基因。现在一般公认的是,存在四个不同的(人)ZP糖蛋白家族ZP1、ZP2、ZP3和ZPB[参照Lefievre等人(2004)Hum.Reprod.19:1580-1586]。根据这种命名法,ZPB糖蛋白现在也称为ZP4。例如,这种命名法应用于Uniprot/SWISSprot、ensEMBL、BLAST(NCBI)、SOURCE、SMART、STRING、PSORT2、CDART、UniGene和SOSUI数据库中,所有这些都在Bioinformatic Harvester(http://harvester.embl.de)中实现。
根据这点,根据由Harris等人提议的命名法,术语ZP1、ZP2、ZP3和ZP4在本文中用于指示四个ZP糖蛋白家族,其中ZP2、ZP3和ZP4分别对应于ZPA、ZPC和ZPB。更特别地,如本文使用的,术语hZP1、hZP2、hZP3和hZP4分别指具有SEQ ID NO.1、SEQ ID NO.2、SEQ ID NO.3和SEQ ID NO.4中列出的多肽主链的蛋白质,及其等位基因变体。
根据本发明,ZP蛋白通常是ZP3蛋白。
在自然界中存在的ZP序列的等位基因变体也被分别的术语ZP和hZP涵盖。等位基因变体包括在起因于单核苷酸多态性(SNP)的特定变体中。SNP可以落入基因的编码序列,基因的非编码区或基因之间的基因间区域内。编码序列内的SNP不一定改变产生的蛋白质的氨基酸序列。其中两种形式均导致相同多肽序列的SNP被称为同义的(有时称为沉默突变)—如果产生了不同的多肽序列,则它们是非同义的。对于待视为SNP的变体,它必须出现在至少1%的群体中。在本发明的上下文中,‘等位基因变体’还可以包括在少于1%的群体中出现的起因于(非同义)突变的多肽序列变体,即起因于点突变、***、缺失等的多肽变体。
因此,根据本发明,术语hZP1、hZP2、hZP3和hZP4分别包括通过较小的序列修饰,不同于SEQ ID NO.1、SEQ ID NO.2、SEQ ID NO.3和SEQ ID NO.4的ZP蛋白。此类修饰包括但不限于:一个或几个氨基酸中的变化,包括缺失(例如,肽的截短形式)、***和/或取代。
‘等位基因变体’在本文中应理解为与SEQ ID NO.1、SEQ ID NO.2、SEQ ID NO.3和SEQ ID NO.4中的任一具有至少90%,优选至少95%,更优选至少97%,还更优选至少98%,还更优选至少99%,还更优选至少99.5%,且最优选至少99.9%的氨基酸序列同一性。
ZP蛋白各自包含将其导入分泌途径内的信号肽,接近羧基末端的透明带结构域和跨膜结构域,随后为短的细胞质尾部。在包括施用与hZP特异性结合的抗体或其片段的本发明的实施方案中,所述抗体或其片段优选针对ZP细胞外结构域。在涉及主动免疫的本发明的实施方案中,可以使用能够诱发针对hZP(原则上包含I类MHC和/或II类MHC限制性T细胞表位的hZP的任何部分)的细胞免疫应答的免疫原性多肽的来源。
hZP3初生蛋白的氨基酸序列含有N端信号肽序列蛋白(SEQ ID NO:3中的氨基酸位置1-22)、保守的“ZP细胞外结构域”(SEQ ID NO:3中的氨基酸位置23-350)、以及前肽(SEQID NO:3中的氨基酸位置351-424),所述前肽由共有弗林蛋白酶切割位点(CFCS;SEQ IDNO:3中的氨基酸位置351-352)、聚合阻断性外部疏水补片(EHP)和C末端跨膜结构域(SEQID NO:3中的氨基酸位置353-424)组成。hZP3信号肽在翻译过程中被切割掉,并且在CFCS处的切割将成熟的hZP3细胞外结构域蛋白(由SEQ ID NO:3中的氨基酸位置23-350组成)与EHP分开,允许其掺入初生的ZP细丝内。因此,成熟的hZP3细胞外结构域的氨基酸主链具有由hZP3的SEQ ID NO:3中的氨基酸位置23-350组成的氨基酸序列。这个细胞外结构域片段在本文中命名为hZP3(23-350)(SEQ ID NO:5)。
在一个优选的实施方案中,本发明涉及通过主动免疫用于治疗对象中的肺癌及其转移的方法。主动免疫的方法优选包括施用免疫原性多肽的来源,其能够诱发针对hZP3或表达hZP3(的任何部分)的细胞的细胞免疫应答、和/或针对hZP3或hZP3(23-350)的体液免疫应答。
免疫原性多肽的来源可以是蛋白质来源、核酸或其组合。蛋白质来源可以例如是包含充当免疫原的一种或多种肽、多肽或蛋白质的组合物。可替代地,免疫原性多肽的来源可以是编码一种或多种免疫原性肽、多肽或蛋白质的核酸分子,当施用于待治疗的对象时,所述核酸分子表达免疫原性肽、多肽或蛋白质。核酸分子可以是DNA、cDNA、RNA、mRNA、其变体、其片段或其组合,如例如WO2014/165291和WO2013/087083中所述。免疫原性多肽的来源可以进一步是表达免疫原性多肽或呈递免疫原性多肽的表位的细胞,优选是活细胞。优选地,所述细胞是微生物,更优选细菌,如例如WO2015/164121中所述的减毒的活单核细胞增多性李斯特菌(Listeria monocytogenes)。可替代地,本发明的免疫原性多肽的细胞来源是自体或同种异体树突状细胞,其在其表面上的HLA分子中呈递免疫原性多肽的至少一个表位。
在一个优选的实施方案中,免疫原性多肽包含选自hZP蛋白的氨基酸序列的邻接氨基酸序列,所述邻接氨基酸序列优选包含I类MHC和II类MHC限制性T细胞表位中的至少一个。更优选地,免疫原性多肽包含选自hZP3蛋白的氨基酸序列(即SEQ ID NO:3)的邻接氨基酸序列,所述邻接氨基酸序列优选包含例如分别选自表2、3和5的I类MHC和II类MHC限制性T细胞表位中的至少一个。更优选地,邻接氨基酸序列包含具有低百分等级的I类MHC和II类MHC限制性T细胞表位中的至少一个(参见Moutaftsi等人,Nat Biotechnol.2006Jul;24(7):817-9;以及Kotturi等人,J Virol.2007May;81(10):4928-40)。具有低百分等级的I类MHC限制性T细胞表位优选是其百分等级不高于1.00、0.80、0.40、0.30、0.20、0.15、0.10或0.05的表位(参见例如表2和5)。具有低百分等级的II类MHC限制性T细胞表位优选是其百分等级不高于2.50、2.40、2.05、2.00、1.80、1.60、1.40、1.20、1.10、1.00、0.90、0.70、0.60、0.50、0.40、0.20.0.15、0.10、0.05或0.02的表位。优选地,邻接氨基酸序列选自来自蛋白水解的hZP3片段的氨基酸序列组的氨基酸序列,所述蛋白水解的hZP3片段由以下组成:N末端信号肽的序列(SEQ ID NO:3中的位置1-22)、成熟细胞外结构域的序列(SEQ ID NO:3中的位置23-350,即SEQ ID NO:5)、以及前肽的序列(SEQ ID NO:3中的氨基酸位置351-424)。此类邻接氨基酸序列的实例在图4中给出,并且此类邻接氨基酸序列的组合在表4中列出。
如包含在免疫原性多肽内的来自hZP(3)蛋白的邻接氨基酸序列,优选包含hZP(3)蛋白的免疫活性(序列)片段。术语“其免疫活性片段”在本领域中一般应理解为指至少包含表位的hZP(3)蛋白抗原的片段,其意指免疫原性多肽至少包含来自hZP(3)蛋白抗原的序列的4、5、6、7或8个邻接氨基酸。根据本发明,该片段至少包含由此类MHC分子呈递给免疫***的MHC I类或MHC II类结合肽。根据本发明的‘免疫活性片段’包含来自ZP蛋白抗原或其同源物或类似物的序列的至少7、8、9、10、11、12、13、14、15、16或17个邻接氨基酸。虽然大多数MHC结合肽具有9个氨基酸的长度,但较长的肽可以通过其中心部分的凸起来容纳(Guo等人,1992,Nature;360(6402):364–366;Speir等人,2001,Immunity;14(1):81–92),导致长度为8至15的结合肽(Schumacher等人,1991,Nature;350(6320):703–706)。表2和5给出了hZP3的序列中的MHC I类结合肽的实例。与II类蛋白质结合的肽在大小方面不受约束(Nelson等人,1999,Rev Immunogenet;1(1):47–59;Yassai等人,2002,J Immunol;168(3):1281–1285),并且可以长11至30个氨基酸不等(Rammensee 1995,Immunogenetics;41(4):178–228),甚至可能是整个蛋白质。然而,结合基序长约9个氨基酸。MHC II类可以容纳比MHC I类长得多的肽,因为MHC II结合槽的末端是开放的,因此表位(结合到槽内)的侧面可以是在任一末端上的另外的氨基酸段。表3中给出了hZP3的序列中的MHC II类结合肽的实例。还更优选地,该片段包含细胞毒性T淋巴细胞(CTL)和辅助T淋巴细胞(HTL)表位两者。然而,最优选地,该片段是需要抗原呈递细胞加工的肽,即该片段具有至少约18个氨基酸的长度,所述18个氨基酸不一定是来自hZP(3)蛋白抗原的邻接序列。
因此,如包含在免疫原性多肽内的来自hZP(3)蛋白的邻接氨基酸序列的长度或免疫原性多肽本身的长度,优选为至少18、19、20、21、22、25、27、30、33或35个氨基酸,并且优选不多于100、80、60、50、45、40、35、33或30个氨基酸。优选地,如包含在免疫原性多肽内的来自hZP(3)蛋白的邻接氨基酸序列的长度或免疫原性多肽本身的长度为19-50或19-45,更优选25-40个氨基酸,甚至更优选25–35且最优选25-30个氨基酸。从可制造性的角度来看,具有约25个氨基酸长度的免疫原性多肽是最佳的,同时仍足够长以含有多重表位且迫使经由抗原呈递细胞的呈递。表4中呈现了此类免疫原性多肽的合适实例,所述免疫原性多肽包含来自hZP3蛋白的邻接氨基酸序列,并且各自包含一种或多种MHC I类和/或MHC II类结合肽。
如本文使用的,术语“其同源物”指通过较少的修饰而不同于天然存在的多肽,但维持天然存在形式的基本多肽和侧链结构的多肽。此类变化包括但不限于:一个或几个氨基酸侧链中的变化;一个或几个氨基酸中的变化,包括缺失(例如肽的截短形式)、***和/或取代;一个或几个原子的立体化学中的变化;和/或较少的衍生化,包括但不限于:甲基化、糖基化、磷酸化、乙酰化、肉豆蔻酰化、异戊烯化、棕榈化、酰胺化和/或糖基磷脂酰肌醇的添加。如本文使用的,同源物或类似物具有与天然存在的多肽相比增强的或基本上相似的功能性。通常,当例如通过使用缺省参数的程序GAP或BESTFIT进行最佳比对时,天然存在的多肽及其同源物共享至少一定百分比的序列同一性。GAP使用Needleman和Wunsch总体比对算法,以在其整个长度上比对两个序列,使匹配数目达到最大并且使缺口数目降到最低。一般地,使用GAP缺省参数,其中缺口产生罚分=8,且缺口延伸罚分=2。对于蛋白质,缺省评分矩阵为Blosum62(Henikoff&Henikoff,1992,PNAS 89,915-919)。序列比对和关于百分比序列同一性的得分可以使用计算机程序进行确定,所述计算机程序例如GCG WisconsinPackage,版本10.3,可从Accelrys Inc.,9685 Scranton Road,San Diego,CA 92121-3752,USA获得。可替代地,可以通过针对数据库例如FASTA、BLAST等搜索,来确定相似性或同一性百分比。
在本文中的同源物应理解为包含免疫原性多肽,其与上文提到的天然存在的ZP多肽具有至少70%,优选至少80%,更优选至少90%,还更优选至少95%,还更优选至少98%,且最优选至少99%的氨基酸序列同一性,并且仍然能够至少诱发由此可获得的免疫应答。同源物或类似物在本文中可以包含取代、***、缺失、另外的N末端或C末端氨基酸、和/或另外的化学部分例如碳水化合物,以增加稳定性、溶解度和免疫原性。
本发明中明确地包括的是包含氨基酸序列的免疫原性多肽的使用,所述氨基酸序列是野生型hZP(3)蛋白的同源物,但由于肿瘤特异性突变(其可能是患者特异性的或共享的)而与其不同,所述肿瘤特异性突变导致改变的氨基酸序列,即所谓的新抗原。
根据本发明,根据本方法施用于人的免疫原性多肽可以是或包含蛋白质或糖蛋白、蛋白质或糖蛋白的消化物和/或其片段,其可以是纯化的形式或可以包含在优选具有生物起源的粗组合物内,例如原核或真核细胞系的裂解产物、超声处理产物或固定物。然而,更优选地,免疫原性多肽是或包含化学合成的(多)肽、或已在体外酶促产生的(多)肽,其可以是纯化的形式或可以包含在粗组合物内。
如本文使用的,术语“表位”指通常由短肽定义的抗原的一部分,当在体内在生理学相关的背景中呈现时,所述部分能够诱发细胞或体液免疫应答。“T细胞表位”指短肽或其一部分,其与MHC分子结合,并且当存在于某些MHC分子中时,被某些T细胞识别。T细胞表位能够经由在异二聚体膜MHC分子中的直接或间接呈递,来诱导细胞介导的免疫应答。优选地,在免疫原性多肽中,至少一个MHC II类限制性表位和至少一个MHC I类限制性表位存在于来自hZP(3)蛋白的氨基酸序列的邻接氨基序列内,由此优选地,MHC II类限制性表位和至少一种MHC I类限制性表位分别选自表3、以及2和5。为了清楚起见,本发明的肽优选包含至少一种MHC I类呈递的表位,并且优选还包含至少一种MHC II类呈递的表位。这些表位各自是可呈递的,并且在已如本文所述进行加工后,与细胞上存在的相应的特定MHC分子结合。每个MHC限制性表位因此也可以被称为MHC结合和/或可呈递的表位。优选地,生成此类表位的C末端的特异性蛋白酶体切割位点确切地存在于表位的氨基酸序列之后,以便从免疫原性多肽中释放并且呈递在MHC I类分子上。长度要求对于MHC II类呈递的表位不那么严格,因此关于II类结合肽的精确酶促生成的需要不那么绝对。简言之,MHC分子优先结合称为“锚”残基的特定氨基酸残基(K.Falk等人,Nature 351:290-96(1991))。这种表征允许在任何已知的肽序列内识别I类和II类MHC结合基序(参见例如表2、5和3)。
在本文上下文中,术语“MHC限制性表位”与T细胞表位同义。如本文使用的,术语“I类MHC限制性表位”指与I类MHC相关的、被细胞毒性T淋巴细胞(也称为CD8+细胞、TCD8或CTL)识别的肽序列。如本文使用的,术语“II类MHC限制性表位”指与II类MHC相关的、被辅助T细胞(也称为CD4+细胞、TCD4或HTL)识别的肽。“B细胞表位”是抗原的一部分,其能够与免疫球蛋白的抗原结合位点结合,并且因此能够无需通过MHC分子的呈递而刺激体液应答。如本文之前说明的,可用于本发明中的多肽或编码所述多肽的核酸包含至少一个T细胞表位。然而,不从本发明中排除还包含B细胞表位的多肽的使用。本免疫原性多肽还可以包括多重T细胞表位以及任选地B细胞表位。当肽中存在多重表位时,所述表位可以串联或者以嵌套或重叠构型定向,其中至少一个氨基酸残基可以被两个或更多个表位共享。
本发明的免疫原性多肽优选包括一种或多种MHC I类限制性表位。如技术人员一般已知的,包含单个MHC限制性表位的抗原仅用于治疗表达MHC等位基因产物的患者的(小)子集,所述MHC等位基因产物能够结合该特定肽。已计算,在人中,含有受HLA-A1、-A2、-A3、-A24和-B7限制的CTL表位的疫苗提供大多数种族背景的大约80%个体的覆盖。因此,如果本方法用于治疗人,则特别优选该方法包括施用包含一种或多种不同多肽的组合物,所述多肽包含选自HLA-A1、HLA-A2、HLA-A3、HLA-A24和HLA-B7限制性表位的一种,更优选两种,最优选三种MHC I类结合的天然ZP,优选hZP3表位;或其同源物。
根据另一个实施方案,本发明的免疫原性多肽优选包括一种或多种MHC II类限制性表位。人中最频繁发现的MHC II类等位基因产物包括HLA-DR1、-DR3、-DR4和-DR7。相应地,优选该方法包括施用包含一种或多种不同多肽的组合物,所述一种或多种不同的多肽包含选自HLA-DR1、HLA-DR3、HLA-DR4和HLA-DR7限制性表位的一种,更优选两种,且最优选三种MHC II类结合的天然ZP,优选hZP3表位;或其同源物。
在另外一个实施方案中,如本文上文和/或分别在表2、5和3中所述,本发明的方法包括施用包含一种或多种多肽的组合物,所述一种或多种多肽包含一种或多种MHC I类限制性表位和一种或多种II类MCH限制性表位;或其同源物。甚至更优选地,所述组合物包含有效量的一种或多种不同的多肽,所述多肽一起包括天然ZP,优选hZP3糖蛋白之一中包含的基本上所有MHC I类和MHC II类结合表位;或者所述一种或多种多肽的同源物。
在一个实施方案中,本方法包括施用包含一种或多种不同免疫原性多肽的组合物。优选地,所述一种或多种不同的多肽一起包含天然ZP,优选hZP3或hZP3(23-350),或者所述一种或多种多肽的同源物中包含的至少50%,更优选至少70%,还更优选至少80%,还更优选至少90%,且最优选至少95%的MHC I类和MHC II类限制性表位。
在一个优选的实施方案中,本方法包括施用组合物,所述组合物包含选自图4中呈现的肽的一种或多种免疫原性肽,例如包含以下或由以下组成的免疫原性肽:SEQ IDNO.66–75中的一种或多种的氨基酸序列。因此,组合物可以包含一种免疫原性肽,所述免疫原性肽包含选自SEQ ID NO.66–75的氨基酸序列或由其组成。然而,优选地,组合物包含至少两种免疫原性肽的组合,所述免疫原性肽包含选自SEQ ID NO.66–75的氨基酸序列或由其组成。特别地,组合物包含免疫原性肽的组合、或SEQ ID NO.66–75中的所有10种的组合,所述免疫原性肽包含选自表4列出的序列组合的氨基酸序列或由其组成。
在一个进一步优选的实施方案中,本方法包括施用包含一种或多种免疫原性肽的组合物,所述免疫原性肽包含选自表5中呈现的表位(即SEQ ID NO.76-85)的表位或由其组成。因此,组合物可以包含一种免疫原性肽,所述免疫原性肽包含选自SEQ ID NO.76-85的氨基酸序列或由其组成。然而,优选地,组合物包含至少两种免疫原性肽的组合,所述免疫原性肽包含选自SEQ ID NO.76-85的氨基酸序列或由其组成。特别地,组合物包含免疫原性肽的组合、或SEQ ID NO.76-85中的所有10种的组合,所述免疫原性肽包含选自表6列出的序列组合的氨基酸序列或由其组成。特别优选的组合物包含一种或多种或所有免疫原性肽,所述免疫原性肽包含SEQ ID NO.79、80、81、83和84的氨基酸序列或由其组成。
在一个优选的实施方案中,本方法包括施用免疫原性多肽的来源,所述多肽包含天然ZP,优选hZP3或hZP3(23-350)糖蛋白的完整氨基酸主链的至少50%,更优选至少70%,还更优选至少80%,还更优选至少90%,且最优选至少95%;或所述多肽的同源物。
在一个特别优选的实施方案中,本方法包括施用包含免疫原性多肽的来源的组合物,所述多肽包含天然ZP,优选hZP3或hZP3(23-350)或所述多肽的同源物的细胞外结构域的完整氨基酸主链的90、95、97、98、99或100%。如本文之前定义的本免疫原性多肽可以是糖基化的。不希望受理论束缚,假设通过这些多肽的糖基化,至少在它们诱发体液(B细胞应答)的方面,其免疫原性是增加的。因此,本文之前定义的免疫原性多肽优选是糖基化的,基于糖蛋白或糖基化多肽的总重量,具有从10-80、15-70或20-60重量%不等的碳水化合物含量。优选地,所述糖基化的免疫原性多肽包含与人的相应天然透明带ZP糖蛋白相似的糖基化模式。
在另一个特别优选的实施方案中,该方法包括施用免疫原性多肽的来源,其为包含有效量的天然ZP,优选hZP3或hZP3(23-350)糖蛋白的多个不同的重叠多肽片段的组合物,所述不同的重叠多肽片段为长度18-60个氨基酸,并且一起包含所述天然ZP或所述天然ZP,优选hZP3或hZP3(23-350)或所述多肽的同源物的细胞外结构域的完整氨基酸主链的至少50%,更优选至少70%,还更优选至少80%,还更优选至少90%,且最优选至少95%。更优选地,不同的重叠多肽片段为长度25-40个氨基酸,甚至更优选25-35个氨基酸,且最优选25-30个氨基酸。通常,在不同的连续18-60个氨基酸多肽片段之间的氨基酸序列重叠是至少7个氨基酸,优选至少8个,更优选至少9个,且最优选至少10个氨基酸。
已描述了关于最常见的MHC I类和II类等位基因的MHC结合基序。这些基序详细列举了氨基酸残基,其充当关于特定I类和II类MHC等位基因的MHC结合锚。考虑到MHC结合锚以及肽的氨基酸序列的复杂的基于计算机的算法,用于预测且定量肽/MHC相互作用的结合亲和力。因此,根据透明带蛋白的已知氨基酸序列的输入,这些算法列出了所有潜在的T细胞表位,各自具有其相应的预测结合得分(参见例如表2、5和3)。用于这些目的的通常已知的生物信息学工具包括例如HLA_BIND(Parker等人,1994,J.Immunol.152:163),SYFPEITHI(Rammensee等人,1995,Immunogenetics 41,178-228;Rammensee等人,Landes Bioscience1997,International distributor:Springer Verlag GmbH&Co.KG,Heidelberg,Germany;http://www.syfpeithi.de/),NetMHC(Buus等人,2003,Tissue Antigens.,62:378-84;Nielsen等人,2003,Protein Sci.,12:1007-17;Nielsen等人,2004,Bioinformatics,20(9):1388-97;http://www.cbs.dtu.dk/services/NetMHC/),TEPITOPE 2000(Sturniolo等人,1999,Nature Biotechnology 17,555-562;http://www.vaccinome.com/pages/597444/),以及(不断更新的)IEDB分析资源–T细胞表位预测工具:http://tools.iedb.org/main/tcell/。
可替代地,技术人员能够使用标准实验(Current Protocols in Immunology,Wiley Interscience 2004),通过实验确定HTL和CTL结合表位。在一个优选的实施方案中,该方法包括施用组合物,所述组合物包含有效量的天然ZP,优选hZP3或hZP3(23-350)糖蛋白的长度为18-100个氨基酸的多个不同多肽片段,其中每个多肽片段包含所述预测的潜在MHC I或MHC II限制性表位中的一种或多种。优选地,不同多肽片段中的所述预测的潜在的MHC I或MHC II限制性表位的氨基酸序列不重叠。优选地,多个不同的多肽片段共同包含通过上述生物信息学工具中的一种或多种预测的至少50、70、80、90或95%的潜在的MHC I或MHC II表位。
在一些情况下,已观察到相同的肽可以结合几种MHC I或II等位基因产物(参见例如表2、5和3)。在一个实施方案中,在本方法中使用此类‘混杂’MHC结合肽是特别优选的。
本免疫方法优选包括施用免疫原性活性多肽片段的来源,所述多肽片段选自如上文之前定义的透明带蛋白片段和/或其同源物,所述多肽片段包含受各种HLA分子限制的CTL和/或HTL表位,并且所述片段为长度18至45个氨基酸。如WO 02/070006中所述,已观察到长度为18至45个氨基酸的肽提供优异的免疫原性特性。肽可以有利地是化学合成的,并且可以任选地是(部分)重叠的,和/或也可以与其它分子、肽或蛋白质连接。将化学部分或另外的(修饰的或D-)氨基酸加入肽的氨基或羧基末端也可以是有利的,以便增加肽的稳定性和/或降低其生物可降解性。为了改善免疫原性/免疫刺激特性,部分可以通过脂化、延长和/或缀合(参见下文)进行附着。肽可以例如通过添加带电荷的或极性的氨基酸来延长,以便增加其在体内的溶解度和/或增加其稳定性。
为了免疫目的,本发明的上述免疫原性多肽也可以与蛋白质融合,所述蛋白质例如但不限于破伤风毒素/类毒素、白喉毒素/类毒素或其它载体分子。本发明的多肽还可以有利地与作为用于免疫显性肽的载体的热休克蛋白融合,所述热休克蛋白例如重组内源性(鼠)gp96(GRP94),如(参考文献:Rapp UK和Kaufmann SH,Int Immunol.2004 Apr;16(4):597-605;Zugel U,Infect Immun.2001;69(6):4164-7)中所述,或具有Hsp70的融合蛋白(Triebel等人;WO99/54464)。本发明的免疫原性多肽也可以与如下文列出的具有佐剂活性的分子,特别是如下文列出的TLR配体/激动剂缀合。
本发明的本免疫原性(多)肽的各个氨基酸残基可以通过肽键或肽键模拟物掺入肽中。本发明的肽键模拟物包括本领域技术人员众所周知的肽主链修饰。此类修饰包括酰胺氮、α-碳、酰胺羰基的修饰,酰胺键的完全替换,延伸,缺失或主链交联。一般参见Spatola,Chemistry and Biochemistry of Amino Acids,Peptides and Proteins,第VII卷(Weinstein编辑,1983)。几种肽主链修饰是已知的,这些包括ψ[CH2S]、ψ[CH2NH]、ψ[CSNH2]、ψ[NHCO]、ψ[COCH2]和ψ[(E)或(Z)CH=CH]。上文使用的命名法遵循由Spatola上文建议的那种。在本文中,ψ指示酰胺键的不存在。替换酰胺基的结构在括号内指定。
氨基酸模拟物也可以掺入多肽内。如本文使用的,“氨基酸模拟物”是除天然存在的氨基酸外的部分,其在构象上和功能上充当关于本发明多肽中氨基酸的取代物。如果此类部分不干扰肽诱发针对天然ZP T细胞表位的免疫应答的能力,则它充当关于氨基酸残基的取代物。氨基酸模拟物可以包括非蛋白质氨基酸,例如β-、γ-、δ-氨基酸,β-、γ-、δ-亚氨酸(例如哌啶-4-羧酸),以及L-α-氨基酸的许多衍生物。许多合适的氨基酸模拟物是技术人员已知的,它们包括环己基丙氨酸、3-环己基丙酸、L-金刚烷基丙氨酸、金刚烷乙酸等等。适合于本发明的肽的肽模拟物由Morgan和Gainor,(1989)Ann.Repts.Med.Chem.24:243-252进行讨论。
根据一个优选的实施方案,本方法包括施用组合物,所述组合物包含如本文上文定义的一种或多种本免疫原性多肽和至少一种赋形剂。赋形剂是药学领域众所周知的,并且可以例如在教科书中如Remington’s pharmaceutical sciences,Mack Publishing,1995中找到。
在另一个优选的实施方案中,待施用的本发明的免疫原性多肽的来源包含编码免疫原性多肽的核酸分子。包含编码免疫原性多肽的核酸分子的来源或组合物可以包含一种或多种不同的核酸分子,其编码如本文上文定义的免疫原性多肽、多肽片段和/或肽中的任何一种。另外,核酸分子可以编码天然ZP的较大部分。核酸分子可以例如编码多肽,所述多肽包含ZP,优选hZP3,更优选hZP3(23-350)或所述多肽的同源物的完整氨基酸主链的至少50、70、80、90、95或100%。优选地,核酸分子编码完整氨基酸主链的至少50、70、80、90、95或99%的邻接段。核酸分子也可能编码来自如上文定义的hZP(3)的邻接氨基酸序列的多于一个(含有T细胞表位的)免疫活性片段,由此在编码的氨基酸序列中,不同的免疫活性片段可以被间隔物或接头序列分开,如串上的珠。
编码本发明的免疫原性多肽的核酸分子可以是DNA分子,优选遗传构建体,其中编码免疫原性多肽的核苷酸序列(cDNA)可操作地连接至适当的表达调节序列,其确保免疫原性多肽在人对象中的靶细胞中的功能性表达,例如包括至少一个强(例如病毒)启动子。用作DNA疫苗的遗传构建体,包括例如质粒或病毒载体,尤其在WO2014/165291、WO2016/123285和WO2017/136758中描述。可替代地,编码本发明的免疫原性多肽的核酸分子可以是RNA分子,例如mRNA、ssRNA、dsRNA或其组合。RNA分子可以例如在包含该分子的颗粒中配制。基于RNA的疫苗的合适实施方案例如在WO2013/087083中描述。
关于核酸疫苗的施用途径包括但不限于肌内、鼻内、腹膜内、真皮内、皮下、静脉内、动脉内、眼内和经口,以及局部,经皮,通过吸入或栓剂,或粘膜组织,如通过对***、直肠、尿道、颊和舌下组织灌洗。优选的施用途径包括肌内、腹膜内、真皮内和皮下注射。可以通过手段包括但不限于电穿孔方法和装置、传统的注射器、无针注射装置或“微弹轰击基因枪(micro projectile bombardment gone gun)”,来施用遗传构建体。
本发明的免疫原性多肽的来源可以进一步是表达和/或呈递免疫原性多肽的活细胞。该细胞可以是自体或同种异体的免疫细胞,例如衍生自待治疗的对象的树突状细胞,或该细胞可以是微生物细胞,更优选细菌,例如减毒的活单核细胞增多性李斯特菌。表达的免疫原性多肽优选是如上文定义的免疫原性多肽。免疫原性多肽可以作为融合蛋白的部分表达,其中优选地,免疫原性多肽融合至对于生物为内源性的蛋白,例如单核细胞增多性李斯特菌LLO或ActA蛋白的N末端片段。关于基于李斯特菌属的疫苗的合适实施方案例如在WO2015/164121中描述。表达本发明的免疫原性多肽的细菌可以经口或肠胃外,优选静脉内施用。
在本发明的另一个实施方案中,本发明的免疫原性多肽的来源是自体或同种异体树突状细胞(DC),其在其表面上的HLA分子中呈递免疫原性多肽的至少一个MHC限制性表位。此类树突状细胞可以例如通过使来自患者的血液的DC(例如从来自患者/对象的单核细胞中分离的DC)与组合物接触和/或负载有组合物进行离体制备,所述组合物包含本发明的免疫原性多肽。与单核细胞或DC接触的免疫原性多肽优选是如上文定义的免疫原性多肽。可以使用促进DC收获的药剂,例如ProgenipoietinTM(Monsanto,St.Louis,Mo.)或GM-CSF/IL-4。在用肽对DC脉冲并洗涤以去除未结合的肽后,将DC重新输注到患者内。在这个实施方案中,提供的是包含肽脉冲的DC的组合物,所述肽脉冲的DC在其表面上的HLA分子中呈递脉冲的肽表位。可替代地,代替使用衍生自对象的自体细胞,可以使用衍生自前体人树突细胞系并且设计为递送肿瘤相关抗原的同种异体DC,例如WO2009/019320、WO2014/090795和WO2014/006058中描述的。采用离体肽脉冲的DC诱导免疫应答的方法是技术人员众所周知的。
本免疫方法可以进一步包括至少一种佐剂的施用,优选共施用。佐剂可以包含疫苗接种领域中已知的任何佐剂,并且可以使用教科书如Current Protocols inImmunology,Wiley Interscience,2004进行选择。
佐剂在本文中预期包括任何物质或化合物,当与抗原组合使用以免疫人或动物时,所述物质或化合物刺激免疫***,从而激发、增强或促进针对抗原的免疫应答,优选不生成对佐剂本身的特异性免疫应答。与在相同条件下但不存在佐剂的情况下针对抗原生成的免疫应答相比,优选的佐剂将针对给定抗原的免疫应答增强至少1.5、2、2.5、5、10或20倍。用于确定在一组动物或人中,如通过佐剂产生的针对给定抗原的免疫应答超过相应对照组的统计平均增强的测试是本领域可用的。佐剂优选能够增强针对至少两种不同抗原的免疫应答。本发明的佐剂通常是对于人是外来的化合物,从而排除了对于人是内源性的免疫刺激性化合物,例如白介素、干扰素和其它激素。
许多佐剂是本领域技术人员众所周知的。合适的佐剂包括例如粒细胞巨噬细胞集落刺激因子(GM-CSF)、不完全弗氏佐剂(IFA)、MontanideTM ISA-51、MontanideTM ISA 720(由Seppic,法国生产的佐剂)、α-半乳糖神经酰胺、明矾、磷酸铝、氢氧化铝、N-乙酰基-胞壁酰基-L-苏氨酰-D-异谷氨酰胺(thr-MDP)、N-乙酰基-正-胞壁酰基-L-丙氨酰-D-异谷氨酰胺(CGP 11637,也称为nor-MDP)、N-乙酰基胞壁酰基-L-丙氨酰-D-异谷氨酰胺基-L-丙氨酸-2-(1'-2'-二棕榈酰-sn-甘油-3-羟基-磷酰氧基)-乙胺(CGP 19835A,称为MTP-PE)、DDA(2二甲基二十八烷基溴化胺)、聚IC、聚-A-聚-U、RIBITM、GERBUTM、Pam3TM、CarbopolTM、SpecolTM、TitermaxTM、破伤风类毒素、白喉类毒素、脑膜炎球菌外膜蛋白、白喉蛋白CRM197。优选的佐剂包含被抗原呈递细胞上存在的Toll样受体(TLR)识别的配体。被TLR识别的各种配体是本领域已知的,并且包括例如脂肽(参见例如WO 04/110486)、脂多糖、肽聚糖、脂磷壁酸、脂***甘露聚糖、脂蛋白(来自支原体或螺旋体)、双链RNA(聚I:C)、聚ICLC(HiltonolTM、由Oncovir,Inc.,USA生产)、未甲基化的DNA、鞭毛蛋白、含有CpG的寡核苷酸、Pam3CysSK4和咪唑并喹啉、以及具有化学修饰的这些配体的衍生物。聚I:C的使用是特别优选的。
对于治疗应用,将本免疫原性多肽,编码其的核酸序列,表达或呈递其的细胞,或者包含这些多肽、核酸序列或细胞的本组合物,施用于患有肺癌及其可能转移的患者、或已接受本文之前所述的治疗肺癌的其它方法的患者,其量足以诱导针对天然ZP糖蛋白和表达ZP蛋白的组织细胞的原发性自身免疫应答。足以实现这点的量定义为“治疗有效”或“预防有效”剂量。此类有效剂量取决于各种因素,包括患者的状况和一般健康状况。因此,可以由受过训练的医务人员确定且调整剂量方案,以提供最佳的治疗或预防效应。
在本方法中,通常以约1、2、5、10、20、50、100、200、500或1000μg/免疫原性多肽或核酸分子或更多的剂量施用一种或多种免疫原性多肽至少一次。优选地,剂量的施用以2、3或4周的间隔重复一次、两次、三次或更多次。
根据一个优选的实施方案,通常的剂量方案包括施用1-1000μg的剂量/肽/免疫,更优选10-500μg/肽/免疫,还更优选5-150μg/肽/免疫的剂量至少一次。优选地,剂量的施用以2、3或4周的间隔重复一次、两次、三次或更多次。根据一个优选的实施方案,施用5-150μg/肽/免疫,并且在2-3周内重复一次或多次/治疗。
本方法优选包括经由肠胃外或经口途径,优选肠胃外途径施用本免疫原性多肽和包含其的组合物。优选的施用途径包括但不限于肿瘤内、肌内、鼻内、腹膜内、真皮内、皮下、静脉内、动脉内、眼内和经口,以及局部,经皮,通过吸入或栓剂,或粘膜组织,如通过对***、直肠、尿道、颊和舌下组织灌洗。优选的施用途径包括肌内、腹膜内、真皮内和皮下注射。在另一个实施方案中,施用是进入引流到***盆内的解剖部位内。在另一个实施方案中,施用是进入多重***盆内。
特别优选的是根据本发明的药剂的真皮内和皮下施用的组合。表皮中的DC明显不同于真皮和皮下组织中的DC。皮内(真皮内)免疫引起表皮DC(Langerin阳性朗格汉斯细胞)的抗原加工和激活,所述表皮DC通过其树突状网络与角质形成细胞紧密接触。这还最佳地激活在朗格汉斯细胞与角质形成细胞之间的相互作用中的炎症途径,随后将负载抗原且激活的朗格汉斯细胞运输至皮肤引流***。皮下施用将激活其它DC子集,所述亚群也变得负载有抗原并且独立地行进至皮肤引流***。可以想象,既可以真皮内施用又可以皮下施用的药剂的使用,可以导致通过不同的DC子集协同刺激这些引流***中的T细胞。
根据本发明的药剂具有另一个优点,其为通过真皮内施用少量的药剂,优选如本文较早定义的肽,仍可以实现免疫原性效应。使用的每种肽的量优选范围为0.3至1000μg,更优选1至500μg,甚至更优选5至150μg。本发明的另一个方面涉及药物制剂,其包含如本文之前定义的本多肽来源作为活性成分。更特别地,药物制剂包含以下作为活性成分:选自ZP蛋白、其同源物以及所述ZP蛋白及其同源物的片段的一种或多种上述免疫原性多肽,或者可替代地,如本文上文定义的基因治疗载体。
根据第一个实施方案,提供了药物制剂,其包含一种或多种本发明的免疫原性多肽。所述多肽在药物组合物中的浓度可以广泛变化,即从按重量计小于约0.1%,通常为按重量计至少约1%到按重量计高达20%或更高。
除活性成分之外,组合物优选至少还包含药学上可接受的载体。药物载体可以是适合于将免疫原性多肽或基因治疗载体递送至患者的任何相容的无毒物质。对于多肽,无菌水、乙醇、脂肪、蜡和惰性固体可以用作载体。药学上可接受的佐剂、缓冲剂、分散剂等等也可以掺入药物组合物内。
根据一个特别优选的实施方案,本发明的药物组合物包含佐剂,如本文之前更详细地定义的。用于掺入本组合物中的佐剂优选地选自被存在于抗原呈递细胞上的Toll样受体(TLR)识别的配体,包括脂肽(参见例如WO 04/110486)、脂多糖、肽聚糖、脂磷壁酸、脂***甘露聚糖、脂蛋白(来自支原体或螺旋体)、双链RNA(聚I:C)、未甲基化的DNA、鞭毛蛋白、含有CpG的DNA、Pam3cysSK4和咪唑并喹啉、以及具有化学修饰的这些配体的衍生物。技术人员能够确定待掺入本药物制剂中的这些佐剂中的任何一种的确切量,以便致使其足够免疫原性。根据另一个优选的实施方案,本药物制剂可以包含一种或多种另外的成分,其用于增强CTL免疫性,如本文之前说明的。
本发明的药剂的制剂,例如包含免疫原性多肽的来源的组合物,施用方式和药学上可接受的赋形剂的使用是本领域已知和习惯的,并且例如在“Remington:The Scienceand Practice of Pharmacy”(编辑,Allen,L.V.第22版,2012,www.pharmpress.com)中描述。
可以使用重组技术来制备用于在本发明中使用的免疫原性多肽、编码其的核酸或表达其的细胞,所述重组技术例如在以下中描述的:Ausubel等人,“Current Protocols inMolecular Biology”,Greene Publishing and Wiley-Interscience,New York(1987),以及Sambrook和Russell(2001)“Molecular Cloning:A Laboratory Manual”(第3版),ColdSpring Harbor Laboratory,Cold Spring Harbor Laboratory Press,New York;这两者均整体引入本文作为参考。还参见Kunkel(1985)Proc.Natl.Acad.Sci.82:488(描述了定点诱变),以及Roberts等人(1987)Nature 328:731-734或Wells,J.A.等人(1985)Gene 34:315(描述了盒诱变)。然而,更优选地,本发明的免疫原性多肽或编码其的核酸通过化学合成进行制备。肽或核酸的化学合成是常规实践,并且各种合适的方法是技术人员已知的。肽或核酸的化学合成也克服了与重组生产相关的问题,所述重组生产更难以标准化,并且需要广泛的纯化和质量控制措施。
在再一个进一步方面,本发明涉及包含结合MHC-肽复合物的T细胞受体的T细胞,其中所述肽优选是包含以下或由以下组成的肽:包含在天然ZP,优选hZP3或hZP3(23-350),或所述一种或多种多肽的同源物中的MHC I类和MHC II类限制性表位。此类T细胞可以例如在包括以下的方法中获得:使T细胞与表达编码本发明的免疫原性多肽的多核苷酸的抗原呈递细胞接触,和/或使T细胞与负载有本发明的免疫原性多肽的抗原呈递细胞接触;以及任选地,培养所述T细胞。抗原呈递细胞(APC),优选是树突状细胞(DC)。T细胞优选是CD8+细胞毒性T细胞或CD4+T辅助细胞。可以使用本领域技术人员已知的任何方法,将编码免疫原性多肽的多核苷酸引入APC或DC内,优选使用转染将根据本发明的多核苷酸引入APC或DC内。优选地,编码免疫原性多肽的多核苷酸提供有适当的控制序列,或包含在适当的表达载体中。使T细胞与本发明的免疫原性多肽接触可以通过本领域技术人员已知的任何方法执行。优选地,免疫原性多肽或包含在免疫原性多肽中的表位通过APC,优选DC的表面上的MHCI类或MHC II类分子,呈递给CD8+细胞毒性T细胞或CD4+T辅助细胞。本领域技术人员知道如何使APC或DC负载有肽。培养所述T细胞可以使用本领域技术人员已知的任何方法来执行。在保持细胞存活的条件下维持T细胞在本文中也应被解释为培养。优选地,使根据本发明的这个方面的T细胞与如本发明的第一个方面中定义的根据本发明的免疫原性多肽接触。用于获得且激活肿瘤抗原特异性T细胞的离体方法在例如WO2017/173321中更详细地描述。在这个方面,本发明还涉及包含根据本发明的(活化的)T细胞的组合物,以及用于治疗性和/或预防性治疗肺癌和/或转移的本发明的方法,所述方法包括向对象施用治疗有效量的本文所述的或通过本文所述的方法产生的(活化的)肿瘤特异性T细胞(参见例如实施例4)。在实施方案中,施用包括施用约106至1012、约108至1011、或约109至1010个(活化的)肿瘤特异性T细胞。该T细胞或其组合物优选经由静脉内、腹膜内、肿瘤内、真皮内或皮下施用进行施用。在另一个实施方案中,将T细胞或其组合物施用到引流到***盆内的解剖部位内。在另一个实施方案中,施用是进入多重***盆内。
本发明的一个进一步方面涉及通过施用与人透明带(hZP)蛋白的表位特异性结合的抗体或其片段,用于治疗或诊断对象中的肺癌及其转移的方法,优选地所述抗体或其片段与hZP3或hZP3(23-350)的表位特异性结合。
“结合”目的抗原,例如肿瘤相关的hZP蛋白抗原或其表位的抗体是这样的抗体,其以足够的亲和力结合抗原,使得所述抗体可用作靶向表达该抗原的细胞或组织的治疗剂,并且不与其它蛋白质显著地交叉反应。在此类实施方案中,如通过荧光激活细胞分选(FACS)分析或放射性免疫测定(RIA)确定的,抗体与“非靶”蛋白的结合程度是抗体与其特定靶蛋白的结合的小于约10%。关于抗体与靶分子的结合,术语“特异性结合”或“特异性结合至”或“特异于”特定多肽或特定多肽靶上的表位,意指可测量地不同于非特异性相互作用的结合。可以例如通过确定与对照分子的结合相比的分子结合来测量特异性结合,所述对照分子一般是不具有结合活性的具有相似结构的分子。例如,特异性结合可以通过与类似于靶的对照分子竞争来确定,所述对照分子例如是过量的未标记靶。在这种情况下,如果标记的靶与探针的结合被过量的未标记的靶竞争性抑制,则指示特异性结合。如本文使用的,术语“特异性结合”或“特异性结合至”或“特异于”特定多肽或特定多肽靶上的表位,可以例如通过分子来显示出,所述分子对于靶具有至少约10-4M,可替代地至少约10-5M,可替代地至少约10-6M,可替代地至少约10-7M,可替代地至少约10-8M,可替代地至少约10-9M,可替代地至少约10-10M,可替代地至少约10-11M,可替代地至少约10-12M或更大的Kd(其可以如下所述进行确定)。在一个实施方案中,术语“特异性结合”指其中分子结合至特定多肽或特定多肽上的表位,而基本上不结合至任何其它多肽或多肽表位。
"Kd"或“Kd值”可以通过使用表面等离振子共振测定进行测量,所述测定使用BIAcoreTM-2000或BIAcoreTM-3000(BIAcore,Inc.,Piscataway,NJ),在25℃下,具有以~10–50应答单位(RU)的固定的抗原CM5芯片。简言之,根据供应商的说明书,用N-乙基-N’-(3-二甲基氨基丙基)-碳二亚胺盐酸盐(EDC)和N-羟基琥珀酰亚胺(NHS),激活羧甲基化的右旋糖酐生物传感器芯片(CM5,BIAcore Inc.)。抗原用10mM乙酸钠pH 4.8稀释成5μg/ml(~0.2μM),然后以5μl/分钟的流速注射,以达到大约10个应答单位(RU)的偶联蛋白。在抗原注射之后,注射1M乙醇胺以封闭未反应的基团。为了动力学测量,抗体或Fab的两倍连续稀释物(0.78nM至500nM)在25℃下以大约25μl/分钟的流速注入具有0.05%Tween 20的PBS(PBST)中。通过同时拟合结合和解离传感图,使用简单的一对一兰米尔结合模型(BIAcoreEvaluation Software版本3.2),计算结合速率(kon)和解离速率(koff)。平衡解离常数(Kd)计算为比率koff/kon。参见例如,Chen,Y.等人,(1999)J.Mol Biol 293:865-881。如果结合速率通过上文的表面等离振子共振测定超过106M-1S-1,则可以通过使用荧光猝灭技术来确定结合速率,所述荧光猝灭技术测量在渐增浓度的抗原的存在下,在25℃下,在PBS,pH 7.2中的20nM抗抗原抗体(Fab形式)的荧光发射强度(激发=295nm;发射=340nm,16nm带通)中的增加或降低,如在分光光度计中测量的,所述分光光度计例如配备停流的分光光度计(AvivInstruments)、或具有搅拌红色比色杯的8000系列SLM-Aminco分光光度计(ThermoSpectronic)。也可以使用如上所述的BIAcoreTM-2000或BIAcoreTM-3000(BIAcore,Inc.,Piscataway,NJ),用上文所述的相同的表面等离振子共振技术,来确定根据本发明的“结合速率(on-rate)”或“结合的速率”或“结合速率(association rate)”或"kon"。
如本文使用的,术语“抗体”在广义上意指并且指任何类型的免疫球蛋白分子,包括多克隆抗体、单克隆抗体(包括鼠、人、人适应的、人源化的和嵌合的单克隆抗体)、抗体片段、双特异性或多特异性抗体、二聚体、四聚体或多聚体抗体、以及单链抗体。
本发明的一个实施方案涉及用于治疗对象中的肺癌及其转移的治疗方法的方法,所述方法包括向所述对象施用包含抗ZP抗体,优选抗hZP3或抗hZP3(23-350)抗体的组合物,其中所述抗体通过抗体依赖性细胞介导的细胞毒性(ADCC)、抗体依赖性细胞吞噬作用(ADCP)、补体依赖性细胞毒性(CDC)或细胞凋亡,来诱导诱导肺癌细胞的杀死。如本领域普通技术人员一般理解的,这些抗体效应子功能可以由抗体的Fc部分介导,例如通过Fc效应子结构域与具有吞噬或裂解活性的免疫细胞上的Fc受体的结合,或通过Fc效应子结构域与补体***的组分的结合。通常,由Fc结合细胞或补体组分介导的效应最终导致靶细胞,即表达ZP的细胞的抑制和/或耗尽。人IgG同种型IgG1、IgG2、IgG3和IgG4显示出关于效应子功能的不同的能力。ADCC可以由IgG1和IgG3介导,ADCP可以由IgG1、IgG2、IgG3和IgG4介导,而CDC可以由IgG1和IgG3介导。在本文所述的方法中,抗hZP3或抗hZP3(23-350)抗体优选是IgG1、IgG2、IgG3或IgG4抗体。
在本文所述的方法中,抗hZP3或抗hZP3(23-350)抗体通过抗体依赖性细胞毒性(ADCC),来诱导表达ZP3蛋白的肺癌细胞的体外和/或体内杀死。在本文所述的方法中,抗hZP3或抗hZP3(23-350)抗体通过补体依赖性细胞毒性(CDC),来诱导表达ZP蛋白的肺癌细胞的体外和/或体内杀死。在本文所述的方法中,抗hZP3或抗hZP3(23-350)抗体通过抗体依赖性细胞吞噬作用(ADCP),来诱导表达ZP3蛋白的肺癌细胞的体外和/或体内杀死。
在本文所述的方法中,抗hZP3或抗hZP3(23-350)抗体通过细胞凋亡,来诱导表达ZP3蛋白的肺癌细胞的体外和/或体内杀死。
在本文所述的方法中,抗ZP抗体可以以一系列亲和力(KD)结合人ZP。在根据本发明的一个实施方案中,抗ZP抗体以高亲和力与ZP结合,例如其KD等于或小于约10-7M,例如但不限于1-9.9(或者其中的任何范围或值,例如1、2、3、4、5、6、7、8或9)×10-8、10-9、10-10、10-11、10-12、10-13、10-14、10-15或者其中的任何范围或值,如通过本领域技术人员实践的,如通过表面等离振子共振或Kinexa方法确定的。一个示例性亲和力等于或小于1×10-8M。另一个示例性亲和力等于或小于1×10-9M。
用于在本发明中使用的优选抗体是单克隆抗体。合适的(单克隆)抗体可以通过方法生成,筛选且产生,所述方法是本领域众所周知的,并且例如在教科书如“Antibodies:ALaboratory Manual,第二版,由E.A.Greenfield编辑,2014,Cold Spring HarborLaboratory Press中描述。更具体而言,Ranking等人(1998,Development 125,2415-2424)描述了针对hZP3细胞外结构域的C末端肽的单克隆抗体H3.1的生成,所述hZP3细胞外结构域包含SEQ ID NO:3的氨基酸335-350。更优选地,用于在本发明中使用的抗体是人源化的,或者甚至更优选是人单克隆抗体,如可以通过本领域众所周知的方法获得的,例如分别在Olimpieri等人(Bioinformatics.2015;31(3):434–435),以及Sheehan和Marasco(Microbiol Spectr.2015;3(1):AID-0028-2014),以及其中引用的参考文献中描述的。
与ZP蛋白的细胞外结构域,例如hZP3的细胞外结构域,即hZP3(23-350)结合的任何抗体可以用于本发明,所述细胞外蛋白具有SEQ ID NO:5的氨基酸序列。可以用于本发明的合适抗体的实例包括例如具有交叉阻断一种或多种参考抗体的结合能力的抗体,所述参考抗体已知与hZP3(23-350)结合。已知与hZP3(23-350)特异性结合的一种此类参考抗体是由Ranking等人(1998,同上)描述的H3.1抗体,关于其的杂交瘤可在登录号:ATCC CRL-2569下从ATCC获得。
因此,用于在本发明中使用的优选抗体具有交叉阻断至少一种抗体的结合的能力,所述抗体已知特异性结合ZP,优选结合hZP3,更优选结合hZP3(23-350)或所述多肽的同源物。更优选地,该抗体具有交叉阻断H3.1抗体的结合的能力,所述H3.1抗体具有登录号:ATCC CRL-2569。抗ZP抗体交叉阻断参考抗体结合的能力在本文中定义为:当靶分子已首先由抗ZP抗体结合时,将参考抗体与合适靶分子的结合减少至少10、20、50、75、90、95、99、99.9或99.99%的能力,所述靶分子包含ZP、hZP3或hZP3(23-350)氨基酸序列,或反之亦然(即,当靶分子首先由参考抗体结合时,抗ZP抗体的结合减少)。交叉阻断的能力原则上可以使用任何类型的免疫测定来确定,所述免疫测定优选竞争性免疫测定,包括例如ELISA、固相直接或间接放射性免疫测定(RIA)、固相直接或间接酶免疫测定(EIA)、夹心竞争测定(参见Stahli等人,Methods in Enzymology 9:242-253(1983));固相直接生物素-抗生物素蛋白EIA(参见Kirkland等人,J.Immunol.137:3614-3619(1986));固相直接标记的测定、固相直接标记的夹心测定(参见"Antibodies,A Laboratory Manual",第二版,2014;同上);使用I125标记的固相直接标记RIA(参见Morel等人,Molec.Immunol.25(1):7-15(1988));固相直接生物素-抗生物素蛋白EIA(Cheung等人,Virology 176:546-552(1990));以及直接标记的RIA(Moldenhauer等人,Scand.J.Immunol.32:77-82(1990))。通常,此类测定涉及使用结合至固体表面的纯化靶分子、未标记的测试抗体和标记的参考抗体。通过确定在测试抗原结合蛋白的存在下,结合至固体表面的标记的量来测量竞争性抑制。通常,测试抗体以过量存在。
在本文描述的本发明的方法中,抗ZP抗体可以在合适的药物组合物中提供,所述药物组合物包含抗ZP抗体和药学上可接受的载体。合适的媒介物和制剂,包括其它人蛋白质,例如人血清白蛋白,例如在如Remington:The Science and Practice of Pharmacy,第21版,Troy,D.B.编辑,Lipincott Williams and Wilkins,Philadelphia,Pa.2006,Part5,Pharmaceutical Manufacturing,第691-1092页中描述,尤其参见第958-989页。
在本文所述的本发明方法中的抗ZP抗体的施用模式可以是任何合适的途径,例如肠胃外施用,例如真皮内、肌内、腹膜内、静脉内或皮下、肺、经粘膜(经口、鼻内、***内或直肠)、或本领域技术人员了解的其它手段,如本领域众所周知的。在本文所述的本发明方法中的抗ZP抗体可以通过任何合适的途径,例如通过静脉内(i.v.)输注或推注注射肠胃外、肌内或皮下或腹膜内施用于患者。
在本发明的方法中,抗ZP抗体以治疗有效量施用。术语“治疗有效量”指在必要的剂量和时间段内有效达到所需治疗结果的量。治疗有效量可以根据因素而变,所述因素如个体的疾病状态、年龄、性别和重量,以及治疗剂或治疗剂的组合在个体中诱发所需应答的能力。有效治疗剂或治疗剂的组合的示例性指标包括例如,患者的健康状况改善,肿瘤负担的减少,肿瘤生长的阻止或减慢,和/或不存在癌细胞转移至机体中的其它位置。
给予患有肺癌的对象的剂量足以减轻或至少部分地阻止待治疗的疾病(“治疗有效量”),并且有时可以是0.005mg至约100mg/kg,例如约0.05mg至约30mg/kg或约5mg至约25mg/kg,或约4mg/kg、约8mg/kg、约16mg/kg或约24mg/kg,或例如约1、2、3、4、5、6、7、8、9或10mg/kg,但可以甚至更高,例如约15、16、17、18、19、20、21、22、23、24、25、30、40、50、60、70、80、90或100mg/kg。
本发明还涉及通常通过施用组合物,通过靶向疗法用于治疗对象中的肺癌及其转移的方法,所述组合物包含能够与人透明带(hZP)蛋白的表位免疫特异性结合的抗体或其片段,优选能够与人透明带3(hZP3)蛋白的表位免疫特异性结合的抗体或其片段,其中所述抗体或片段是免疫缀合物例如免疫毒素、抗体-药物缀合物或携带放射性同位素的抗体的部分。
术语“免疫缀合物”指其中抗体或其片段与另一种分子化学连接的缀合物。当与抗体或其片段连接的分子是毒素时,免疫缀合物被称为免疫毒素。当与抗体或其片段连接的分子是(细胞毒性)药物时,免疫缀合物经常被称为‘抗体-药物缀合物’。免疫缀合物用于局部递送细胞毒性剂或细胞生长抑制剂(即在癌症的治疗中杀死或抑制肿瘤细胞的药物)的用途,可以允许药物部分靶向递送至肿瘤,以及在其中的细胞内累积,其中这些未缀合的药物试剂的全身施用可以导致对正常细胞以及待寻求消除的肿瘤细胞的不可接受的毒性水平。从而寻求最大限度的功效伴随最低限度的毒性。设计且完善抗体缀合物的努力已集中于单克隆抗体(mAb)的选择性,以及药物连接和药物释放特性。
在一些实施方案中,放射性同位素可以与抗体连接,所得到的免疫缀合物经常被称为免疫放射性同位素。
如本领域技术人员将理解的,抗ZP抗体部分可以是具有本文之前关于被动免疫实施方案描述的任何或所有特征的抗ZP抗体。免疫缀合物还可以包含仅能够与人透明带(hZP)蛋白的表位免疫特异性结合的抗体或其片段,优选能够与人透明带3(hZP3)蛋白的表位免疫特异性结合的抗体或其片段,而不诱导任何效应子机制。
本发明进一步考虑了免疫缀合物,其包含与放射性同位素或放射性核素、或者(能够)含有此类放射性核素的部分缀合的抗体或其片段。本领域技术人员将认识到,存在众多放射性核素,其可以通过众所周知的技术与肿瘤特异性抗体偶联,并且递送至特异性损伤肿瘤细胞和组织的部位。例如,适合于使用的试剂包含125I、123I、111In、177Lu、90Y、213Bi、225Ac和99mTc。在放射性核素中,钇90(90Y)可以特别适合于放射免疫疗法,因为钇90(90Y)提供超过碘131(131I)的优点,因为它向肿瘤递送更高的β能量(2.3MeV相对于0.61MeV),并且具有5至10mm的径长,导致杀死靶向细胞和邻近细胞两者的改善能力,特别是在大块或血管化不良的肿瘤中的优点。
在一个进一步的实施方案中,本发明涉及用于人对象中的肺癌和/或其转移和/或其复发的诊断和/或预后的方法。该方法优选应用于非小细胞肺癌和/或其转移和/或其复发的诊断和/或预后。用于诊断和/或预后的方法优选包括施用抗体或其片段,其特异性结合hZP,优选hZP3或hZP3(23-350)的表位,如本文上文所述。抗体或其片段优选与显像剂或可检测试剂缀合,优选地该试剂是体内显像剂。此类试剂的非限制性实例包括酶、放射性标记、半抗原、荧光标记、磷光分子、化学发光分子、发色团、发光分子、光亲和分子、有色颗粒或配体例如生物素、顺磁性离子、放射性同位素、荧光染料、NMR-可检测物质和X射线显像剂(参见例如US20170240637A1)。
如本文使用的,短语“体内成像”指在整个活的哺乳动物中检测本发明的可检测标记的抗体的存在的方法。可以通过体内成像来检测光学可检测的蛋白质,例如荧光抗体和荧光素酶缀合的抗体。体内成像可以用于提供哺乳动物的2D以及3D图像。例如,可以将放射性标记的抗体施用于对象,并且用γ照相机对对象成像。电荷耦合装置照相机、CMOS或3D断层扫描仪可用于进行体内成像。使用计算机断层摄影术、磁共振成像、超声波检查术、正电子发射断层摄影术、单光子发射计算机断层摄影术(SPECT)等等的体内成像方法是本领域众所周知的。来自如上所述的许多体内成像方法的信息可以提供关于对象中的癌细胞的信息。
在诊断和/或预后方法中,本发明的可检测标记的抗体可以用于确定或多或少顺应本文所述疗法的对象是否患有肺癌和/或其转移和/或其复发。以及监测对象中的治疗进度和/或对疗法的应答。它也可以用于评价其它(组合)疗法的过程。因此,诊断/预后方法可以告知临床医生对疗法和治疗方案的选择。
在本文件及其权利要求中,动词“包括”及其变化形式以其非限制性意义使用,以意指包括在该词之后的项目,但不排除未具体提到的项目。另外,通过不定冠词“一个”或“一种”提及的要素不排除存在多于一个要素的可能性,除非上下文明确要求存在一个且仅存在一个要素。因此,不定冠词“一个”或“一种”通常意指“至少一个/种”。
在下述实施例中进一步说明本发明,所述实施例不预期以任何方式限制本发明的范围。
附图说明
图1:来自三个不同患者的鳞状癌细胞肺癌中的ZP3表达。每个水平泳道代表来自一个单一患者的结果。从左到右分别为苏木精伊红组织病理学(HE x 5);ZP3 mRNA表达的原位杂交(RNA Scope x 40);以及通过免疫组织化学的ZP3蛋白表达(IHX x 20)。丰富ZP3表达唯一地在鳞状癌细胞(SCC;箭头)中检测到,而ZP3表达在基质细胞(S)或健康细胞中并不可见。
图2:来自三个不同患者的腺癌细胞肺癌中的ZP3表达。每个水平泳道代表来自一个单一患者的结果。从左到右分别为苏木精伊红组织病理学(HE x 5);ZP3 mRNA表达的原位杂交(RNA Scope x 40);以及通过免疫组织化学的ZP3蛋白表达(IHX x 20)。丰富ZP3表达唯一地在腺癌细胞(ACC;箭头)中检测到,而ZP3表达在基质细胞(S)或健康细胞中并不可见。
图3:分别作为阳性对照和阴性对照的卵巢(顶部行)和脾(底部行)中的ZP3表达。从左到右分别为苏木精伊红组织病理学(HE x 5);ZP3 mRNA表达的原位杂交(RNA Scope x40);以及通过免疫组织化学的ZP3蛋白表达(IHC x 20)。丰富的ZP3 mRNA在***中检测到,并且ZP3蛋白在人***周围的ZP以及***的细胞质中检测到。在脾中未检测到ZP3 mRNA或蛋白质的表达。
图4:选择的hZP3肽序列。方框和椭圆形分别包围了如表2、5和3中指示的预测的MHC I类和MHC II类结合剂。星号指示潜在的N联糖基化位点,并且序列上方的括号标记具有O联聚糖簇的区域。
图5:用于将hZP3阳性B16-HLA-A2黑色素瘤肿瘤细胞和hZP3肽混合物(包含表5中的肽4、5、6、8和9)或rhZP31-383蛋白施用于HLA-A2转基因小鼠的时间表。在第0天(D0)时,皮下(s.c.)给予具有106个细胞/小鼠的肿瘤注射。其后,施用初免注射7至10天(D7-10),以及在第14天至第17天(D14-17)时的加强注射。在处理后监测肿瘤大小。在第30至35天,处死小鼠以确定hZP3特异性CD8+应答(ELISpot)。
图6:在接受PBS的对照小鼠中、以及在用rhZP31-383蛋白或5种hZP3肽(包含表5中的肽4、5、6、8和9)的组合的2次s.c.免疫后的小鼠中,根据肿瘤攻击后的天数的肿瘤大小(以mm3计)。
图7:在用5种hZP3肽(肽)的混合物免疫后、或在用rhZP31-383蛋白ZP3(prot)免疫后,如针对肽(所有5种或个别地肽4、5、6、8或9)测量的CD8+T细胞应答,如通过干扰素γ(IFNg)ELISpot确定的。
实施例
实施例1
ZP3在人肺癌组织中的表达使用免疫组织化学(IHC)进行确定。来自源于不同患者的肺癌组织的组织微阵列(TMA)得自荷兰的病理学研究所。
用以两种不同浓度的人ZP3单克隆抗体H3.1完成免疫组织化学测定:1.0μg/mL和0.1μg/mL。
含有***的人卵巢切片用作组织阳性对照。另外,脾组织的样品用作阴性对照。
下述IHC方案用于所有样品:
第1天
1.脱石蜡和水合:
a)二甲苯–3x 3分钟,
b)无水EtOH–2x 3分钟,
c)96%EtOH–2x 3分钟,
d)70%EtOH–2x 3分钟
e)dH20–1x 10分钟,
2.抗原回收:
a)在回收器中具有0.05%Tween 20的10mM柠檬酸缓冲液(pH 6.0)共2.5小时
b)冷却
3.在具有0.05%Tween 20的Tris缓冲盐水(TBS)(TBST)中洗涤切片3次,各5分钟。
4.使切片在3%H2O2(在TBS中稀释)中温育15分钟,以在室温(RT)下在黑暗中猝灭内源性过氧化物酶活性。
5.在TBST(具有0.05%Tween 20的TBS)中洗涤切片2次,各5分钟。
6.使切片在1mg/mL硼氢化钠溶液(在TBS中稀释)中温育15分钟,以猝灭游离醛基(RT,在黑暗中,对于IF染色、ZP3共定位更重要)。
7.在TPBS(具有0.05%Tween 20的TBS)中洗涤切片3次,各5分钟。
8.在封闭溶液-在TBST中的3%BSA中温育切片(1小时;RT;加湿室)。
9.使切片与在封闭溶液(TBST中的3%BSA)中稀释的针对hZP3的一抗(1.0、0.125或0.1μg/ml)一起在冷藏室中的加湿室中温育过夜。
第2天
10.在TBST中洗涤切片3次,各5分钟。
11.使切片与抗小鼠DAKO聚合物一起温育30分钟(EnVision#4001)。
12.在TBST中洗涤切片3次,各5分钟。
13.使切片与Chromogen System(DAKO,对于1ml缓冲液#K3468为1滴)一起温育–10分钟,通过将载玻片浸入具有自来水容器中终止反应。
14.使切片在自来水中温育2分钟。
15.在复染前用ddH2O冲洗载玻片
16.将切片在苏木精中复染–20-30秒。
17.使切片在自来水中温育,以去除过量的苏木精。
18.使切片脱水:
a.70%EtOH–2x 3分钟
b.96%EtOH–2x 3分钟
c.无水EtOH–2x 3分钟
d.二甲苯–3x 3分钟
19.用Pertex固定。
在阳性对照中,抗体检测到在人***周围的ZP中的蛋白质。ZP3蛋白也存在于***的细胞质中。当省略一抗时,在肺癌组织样品的切片中未检测到阳性染色。在脾和肝组织中,用ZP单克隆抗体未观察到阳性染色。
在肺癌样品(TMA)中,ZP3的存在通过对于ZP3染色呈阳性的组织区域得到确认,其强度在从不同患者获得的样品中不同(参见表1中的鳞状细胞癌TMA结果)。根据本发明,可以通过用ZP3-抗原的免疫来治疗对于ZP3表达染色呈阳性的此类肿瘤。
实施例2
使用IHC(鳞状细胞癌,n=10和肺腺癌,n=10)和RNA scope原位杂交(鳞状细胞癌,n=4和肺腺癌,n=4)确定ZP3在人肺癌组织中的表达。来自不同患者的组织样品得自波兰的病理学研究所。
用以两种不同浓度的人ZP3单克隆抗体完成免疫组织化学测定。遵循与实施例1所述的相同的IHC方案。
人卵巢的切片用作组织阳性对照。另外,脾组织的样品用作阴性对照。
根据制造商的方案,用RNAscope FFPE 2.0 HD Detection Kit Brown[AdvancedCell Diagnostics(ACD),Hayward,California,USA,CAT#310033],完成***固定的石蜡包埋的(FFPE)人卵巢和癌症样品的原位杂交。
使FFPE切片脱石蜡
1.在通风橱中,用~200ml新鲜的二甲苯装满两个清洁剂皿,并且用200mL新鲜的100%乙醇装满2个清洁剂皿。
2.将载玻片放入第一个含有二甲苯的清洁剂皿中,并且在RT下温育5分钟。通过将载玻片架偶尔在清洁剂皿中上下升降来搅动载玻片。
3.从第一个含有二甲苯的皿中取出载玻片架,然后立即放入通风橱中的第二个含有二甲苯的清洁剂皿中,并且重复温育。
4.从第二个含有二甲苯的皿中取出载玻片架,然后立即放入含有100%乙醇的染色皿中。使载玻片在100%乙醇中在RT下伴随搅动温育1分钟。
5.用新鲜的100%乙醇重复步骤4。
6.从架上取下载玻片,然后将切片面朝上放在吸水纸上。在RT下风干5分钟。
平衡设备
1.打开HybEZTMOVEN,并且将温度设定为40℃。
2.将加湿纸放入湿度控制托盘中,并且用蒸馏水完全润湿。
3.将覆盖的托盘***烤箱内,并且关闭烤箱门。使用前,将托盘在40℃下加热30分钟。
准备1X预处理2
通过将630mL蒸馏水加入1L烧杯中的1瓶(70mL)10X预处理2溶液中,制备700mL新鲜的1X预处理2。充分混合。将含有1X预处理2的烧杯放在加热板上。用箔覆盖烧杯,并且将加热板调高10-15分钟。一旦1X预处理2达到沸腾,将将加热板旋钮旋转到100–104℃,以维持均匀沸腾。
预处理1和2
1.应用预处理以覆盖整个切片,并且在RT下温育10分钟。
2.通过在吸水纸上敲击载玻片,和/或轻拂,一次从一个载玻片中去除预处理1溶液。立即将载玻片***浸没在装满蒸馏水的染色皿中的载玻片架内。
3.在蒸馏水中洗涤载玻片两次。
4.应用预处理2。确保1X预处理2溶液处于温和沸腾。用一把镊子将含有载玻片的载玻片架非常缓慢地浸入沸腾的1X预处理2溶液中。用箔覆盖烧杯,并且将载玻片煮沸15分钟。在预处理时间结束后,使用镊子立即将热载玻片架从1X预处理2转移到含有蒸馏水的染色皿中。不要让载玻片在预处理2中冷却。
5.在蒸馏水中洗涤载玻片两次。
6.通过将支架上下移动3–5次,在新鲜的100%乙醇中洗涤载玻片。使载玻片风干。使用疏水屏障围栏创建疏水屏障。
7.将干燥的载玻片放在载玻片架上,并且添加预处理3以完全覆盖每个切片。从HybEZTM烤箱中取出HybEZTM湿度控制托盘,并且将HybEZTM载玻片架放入托盘中。关闭盖子,并且将托盘插回到烤箱内。
8.使载玻片在40℃下温育30分钟。
9.从烤箱中取出HybEZTM湿度控制托盘。
10.用蒸馏水将载玻片洗涤两次。
11.添加适当的探针以完全覆盖每个切片。
人ZP3探针(目录号442631),关于低丰度转录物的阳性对照探针(Mm-Polr-2a,#312471)和阴性对照探针(DapB,ACD-310043)
将HybEZTM载玻片架放入HybEZTM湿度控制托盘中,用盖子覆盖,并且在40℃下***烤箱内2小时。
12.从烤箱中取出HybEZTM控制托盘,并且取下HybEZTM载玻片架。
13.在1X洗涤缓冲液中在RT下洗涤载玻片2分钟。通过在皿中上下移动载玻片架来搅动载玻片。
14.用新鲜的1X洗涤缓冲液重复步骤13。
15.用Amp 1完全覆盖每个切片,使载玻片在40℃下温育30分钟。
16.在1X洗涤缓冲液中在RT下伴随偶尔的搅动,洗涤载玻片两次2分钟。
17.用Amp 2完全覆盖每个切片,使载玻片在40℃下温育15分钟。
18.在1X洗涤缓冲液中在RT下伴随偶尔的搅动,洗涤载玻片两次2分钟。
19.用Amp 3完全覆盖每个切片,使载玻片在40℃下温育30分钟。
20.在1X洗涤缓冲液中在RT下伴随偶尔的搅动,洗涤载玻片两次2分钟。
21.用Amp 4完全覆盖每个切片,使载玻片在40℃下温育15分钟。
22.在1X洗涤缓冲液中在RT下伴随偶尔的搅动,洗涤载玻片两次2分钟。
23.用Amp 5完全覆盖每个切片,使载玻片在40℃下温育30分钟。
24.在1X洗涤缓冲液中在RT下伴随偶尔的搅动,洗涤载玻片两次2分钟。
25.用Amp 6完全覆盖每个切片,使载玻片在40℃下温育15分钟。
26.在1X洗涤缓冲液中在RT下伴随偶尔的搅动,洗涤载玻片两次2分钟。
27.通过对于每种溶液分配相同的滴数(每种试剂2滴,总共4滴),在适当大小的管中混合等体积的褐色-A和褐色-B(DAB底物)。将DAB吸取到每个组织切片上。确保切片被覆盖,并且在RT下温育10分钟。
28.通过将载玻片架上下移动3–5次,在蒸馏水中洗涤载玻片。用新鲜的蒸馏水替换。
29.将载玻片在50%苏木精染色溶液中在RT下复染2分钟。
30.通过将载玻片架上下移动3–5次,在蒸馏水中洗涤载玻片。继续用新鲜的蒸馏水重复,直到载玻片为透明的,而切片保持紫色。
31.用0.02%的氨水替换染色皿中的蒸馏水。将架上下移动2–3次。切片应该变成蓝色。用蒸馏水替换氨水。洗涤载玻片3-5次。
32.使载玻片脱水(70%乙醇2分钟,100%70%乙醇2分钟,二甲苯5分钟)。
33.用Pertex固定样品。
在阳性对照中,抗体检测到在人***周围的ZP以及***的细胞质中的蛋白质(图3,顶部行IHC x 20)。当省略一抗(未显示)时,在肺癌组织样品的切片中未检测到阳性染色。在脾组织中,用ZP单克隆抗体未观察到阳性染色(图3,底部行IHC x 20)。
在肺癌样品,亚型鳞状细胞癌(图1)和腺癌(图2)中,ZP3的存在通过经由IHC和RNAscope两者对于ZP3染色呈阳性的组织区域得到确认,其强度在从不同患者获得的样品中不同。根据本发明,可以通过用ZP3-抗原的免疫来***,例如对于ZP3表达染色呈阳性的这些肿瘤。
实施例3
使用预测HLA I类和II类肽结合的算法,分析了hZP3序列的HLA I类限制性细胞毒性T细胞(CTL)表位和HLA II类限制性T辅助细胞表位。
使用来自Center for Biological Sequence Analysis(CBS),TechnicalUniversity of Denmark(http://www.cbs.dtu.dk/services/NetCTLpan/)的NetCTLpanServer(Xu等人,2012,Clin Dev Immunol;12:831010),执行MHC I类结合预测。
使用IEDB分析资源共识工具(http://tools.immuneepitope.org/main/html/tcell_tools.html),(Stranzl等人,2010,Immunogenetics;62:357-368;Wang等人,2008,PLoS Comput Biol.4(4):e1000048),进行MHC II类结合预测。这种工具采用不同的方法来预测MHC II类表位,包括将NN-align、SMM-align和组合文库方法相组合的共识方法。低百分等级等于良好的结合剂。
提交的等位基因是属于HLA I类和II类超型的那些(Wang等人,2010,BMCBioinformatics.11:568;Sidney等人,2008,BMC Immunol.;9:1.doi:10.1186/1471-2172-9-1)。MHC分子是极度多态性的,但是,尽管这种多态性,HLA I类分子仍可以聚类成指定为超型的组,代表共享大量重叠的肽结合特异性的分子集合(Wang等人,2010BMCBioinformatics.11:568)。以相同的方式,对于HLA II类限定了七个不同的超型(主要DR、DR4、DRB3、主要DQ、DQ7、主要DP和DP2)(Greenbaum等人,2011,Immunogenetics.;63(6):325-35)。
提交的hZP3肽序列不含信号肽和跨膜结构域,即从aa 23到aa 387。分析结果包含在表2和5(MHC I类配体)研究表3(MHC II类配体)中。
表2和3分别呈现的MHC I类和II类配体充当用于设计本发明的免疫原性肽的指导,例如包含一种或多种多肽的组合物,其中所述一种或多种多肽包含选自表2的一种或多种MHC I类限制性表位、和/或选自表3的一种或多种MCH II类限制性表位。
图4中包含了覆盖用于在临床环境中使用的hZP3序列的一系列hZP3肽。来自表2和表3的预测的MHC I类和II类结合剂序列、以及可能的糖基化位点对于限定该肽已加以考虑,所述肽各自含有具有低百分等级的许多预测的MHC I类和MHC II类结合剂,用于诱导良好的免疫应答。这些hZP3肽片段包括hZP330-78(SEQ ID NO:66)、hZP376-101(SEQ ID NO:67)、hZP399-141(SEQ ID NO:68)、hZP3138-187(SEQ ID NO:69)、hZP3185-225(SEQ ID NO:70)、hZP3224 -267(SEQ ID NO:71)、hZP3257-290(SEQ ID NO:72)、hZP3298-317(SEQ ID NO:73)、hZP3331-357(SEQ ID NO:74)和hZP3358-383(SEQ ID NO:75)。表4列出了用于组成组合物的这些肽片段的组合,所述组合物包含至少两种肽片段的组合。
表2:hZP3蛋白中包含的预测的MHC I类配体。
表3:hZP3蛋白中包含的预测的MHC II类配体。
实施例4
使用计算机芯片(in silico)上的预测软件,已鉴定了来自rhZP3蛋白的潜在HLA-A2限制性T细胞表位。使用的软件是NETMHCPAN 3.0计算机芯片上的预测软件。
表5:来自rhZP3蛋白的HLA-A2限制性T细胞表位。
编号 | 位置 | 肽 | 亲和力(nM) | %等级 | SEQ ID NO |
1 | 115 | FLLHDPRPV | 5.1 | 0.04 | 76 |
2 | 175 | RLMEENWNA | 5.2 | 0.04 | 77 |
3 | 109 | ALVYSTFLL | 21.3 | 0.3 | 78 |
4 | 263 | FTVDVFHFA | 19.9 | 0.3 | 79 |
5 | 174 | LRLMEENWNA | 28.6 | 0.4 | 80 |
6 | 367 | FLDRRGDHEV | 53.2 | 0.7 | 81 |
7 | 239 | CLVDGLTDA | 79.1 | 0.9 | 82 |
8 | 276 | NMIYITCHL | 76.6 | 0.9 | 83 |
9 | 114 | TFLLHDPRPV | 101.9 | 1.1 | 84 |
10 | 64 | KLIRAADLTL | 129.9 | 1.2 | 85 |
已进行了体内临床前功效研究,以评价在用rhZP3多肽(具有his-标签的aa 1-383)和5种不同的ZP3表位免疫后的免疫应答和抗肿瘤应答。基于在先前执行的免疫原性实验(数据未显示)过程中观察到的CD8+T细胞应答,来选择hZP3表位,所述免疫原性实验使用与不同佐剂组合的rhZP3多肽(aa 1-383)和包含如指示的hZP3表位的肽库(参见表5)。肽由Pepscan(荷兰)以纯度>96%合成。
在这个实验中,在治疗环境中,具有ZP3表达肿瘤的HLA-A2转基因小鼠用rhZP3蛋白、hZP3肽库或作为对照的PBS进行处理。
HLA-A2转基因小鼠模型用于这项研究。为了建立肿瘤模型,用rhZP3转染B16-HLA-A2转基因鼠黑色素瘤细胞系(参见Tran等人,Clin Cancer Res,2016;22(16):4133-44中的实施例)。
具有ZP3表达肿瘤的三组雌性HLA-A2转基因小鼠(n=6)用以下进行处理:
1.PBS;
2.5种hZP3肽的库(先前在HLA-A2/DR1小鼠中鉴定的5种占优势的肽,包括表5中鉴定为4、5、6、8和9的表位;0.5nmol/肽),加上作为佐剂的GM-CSF/CpG(20μg GM-CSF和50μgCpG);和,
3.rhZP3蛋白(100μg,s.c.)加上作为佐剂的GM-CSF/CpG(20μg GM-CSF和50μgCpG)。
在第0天(D0)时,给予用106个细胞/小鼠的肿瘤注射(s.c.)。其后,施用初免注射7至10天(D7-10),以及在第14天至第17天(D14-17)时的加强注射。在处理后监测肿瘤大小。在第30至35天,处死小鼠以确定ZP3特异性TCD8+应答(ELISpot)。参见图5中的时间表。
在PBS施用后,肿瘤大小的确增加,而在用rhZP3蛋白或5种hZP3肽的组合的2次s.c免疫后,未观察到肿瘤的生长(参见图6)。
此外,如图7中所示,在用5种hZP3肽免疫后,针对所述肽测量到强CD8+T细胞应答(IFNg)。另外,在用ZP3蛋白免疫后,观察到TCD8应答(参见图7)。
表4.来自图4的氨基酸序列的组合,待掺入免疫原性肽中,用于组成根据本发明的合成长肽的组合物。各种组合通过分号分开。
2种肽的组合
SEQ ID NO.66、SEQ ID NO.67;SEQ ID NO.66、SEQ ID NO.68;SEQ ID NO.66、SEQID NO.69;SEQ ID NO.66、SEQ ID NO.70;SEQ ID NO.66、SEQ ID NO.71;SEQ ID NO.66、SEQID NO.72;SEQ ID NO.66、SEQ ID NO.73;SEQ ID NO.66、SEQ ID NO.74;SEQ ID NO.66、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68;SEQ ID NO.67、SEQ ID NO.69;SEQ ID NO.67、SEQID NO.70;SEQ ID NO.67、SEQ ID NO.71;SEQ ID NO.67、SEQ ID NO.72;SEQ ID NO.67、SEQID NO.73;SEQ ID NO.67、SEQ ID NO.74;SEQ ID NO.67、SEQ ID NO.75;SEQ ID NO.68、SEQID NO.69;SEQ ID NO.68、SEQ ID NO.70;SEQ ID NO.68、SEQ ID NO.71;SEQ ID NO.68、SEQID NO.72;SEQ ID NO.68、SEQ ID NO.73;SEQ ID NO.68、SEQ ID NO.74;SEQ ID NO.68、SEQID NO.75;SEQ ID NO.69、SEQ ID NO.70;SEQ ID NO.69、SEQ ID NO.71;SEQ ID NO.69、SEQID NO.72;SEQ ID NO.69、SEQ ID NO.73;SEQ ID NO.69、SEQ ID NO.74;SEQ ID NO.69、SEQID NO.75;SEQ ID NO.70、SEQ ID NO.71;SEQ ID NO.70、SEQ ID NO.72;SEQ ID NO.70、SEQID NO.73;SEQ ID NO.70、SEQ ID NO.74;SEQ ID NO.70、SEQ ID NO.75;SEQ ID NO.71、SEQID NO.72;SEQ ID NO.71、SEQ ID NO.73;SEQ ID NO.71、SEQ ID NO.74;SEQ ID NO.71、SEQID NO.75;SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.72、SEQID NO.75;SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.74、SEQID NO.75;
3种肽的组合
SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68;SEQ ID NO.66、SEQ ID NO.67、SEQID NO.69;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.70;SEQ ID NO.66、SEQ ID NO.67、SEQID NO.71;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.72;SEQ ID NO.66、SEQ ID NO.67、SEQID NO.73;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69;SEQ ID NO.66、SEQ ID NO.68、SEQID NO.70;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.71;SEQ ID NO.66、SEQ ID NO.68、SEQID NO.72;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.73;SEQ ID NO.66、SEQ ID NO.68、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.69、SEQID NO.70;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.71;SEQ ID NO.66、SEQ ID NO.69、SEQID NO.72;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.73;SEQ ID NO.66、SEQ ID NO.69、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.70、SEQID NO.71;SEQ ID NO.66、SEQ ID NO.70、SEQ ID NO.72;SEQ ID NO.66、SEQ ID NO.70、SEQID NO.73;SEQ ID NO.66、SEQ ID NO.70、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.70、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.71、SEQ ID NO.72;SEQ ID NO.66、SEQ ID NO.71、SEQID NO.73;SEQ ID NO.66、SEQ ID NO.71、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.71、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.66、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.72、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69;SEQ ID NO.67、SEQ ID NO.68、SEQID NO.70;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.71;SEQ ID NO.67、SEQ ID NO.68、SEQID NO.72;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.73;SEQ ID NO.67、SEQ ID NO.68、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQID NO.70;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.71;SEQ ID NO.67、SEQ ID NO.69、SEQID NO.72;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.73;SEQ ID NO.67、SEQ ID NO.69、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.70、SEQID NO.71;SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.72;SEQ ID NO.67、SEQ ID NO.70、SEQID NO.73;SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.74;SEQ ID NO.67、SEQ ID NO.70、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.71、SEQ ID NO.72;SEQ ID NO.67、SEQ ID NO.71、SEQID NO.73;SEQ ID NO.67、SEQ ID NO.71、SEQ ID NO.74;SEQ ID NO.67、SEQ ID NO.71、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.67、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.72、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70;SEQ ID NO.68、SEQ ID NO.69、SEQID NO.71;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.72;SEQ ID NO.68、SEQ ID NO.69、SEQID NO.73;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.74;SEQ ID NO.68、SEQ ID NO.69、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71;SEQ ID NO.68、SEQ ID NO.70、SEQID NO.72;SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.73;SEQ ID NO.68、SEQ ID NO.70、SEQID NO.74;SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.75;SEQ ID NO.68、SEQ ID NO.71、SEQID NO.72;SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.73;SEQ ID NO.68、SEQ ID NO.71、SEQID NO.74;SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.75;SEQ ID NO.68、SEQ ID NO.72、SEQID NO.73;SEQ ID NO.68、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.68、SEQ ID NO.72、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.68、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.69、SEQ ID NO.70、SEQID NO.71;SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72;SEQ ID NO.69、SEQ ID NO.70、SEQID NO.73;SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.74;SEQ ID NO.69、SEQ ID NO.70、SEQID NO.75;SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72;SEQ ID NO.69、SEQ ID NO.71、SEQID NO.73;SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.74;SEQ ID NO.69、SEQ ID NO.71、SEQID NO.75;SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.69、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.75;SEQ ID NO.69、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.69、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.69、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72;SEQ ID NO.70、SEQ ID NO.71、SEQID NO.73;SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.74;SEQ ID NO.70、SEQ ID NO.71、SEQID NO.75;SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.70、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.75;SEQ ID NO.70、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.70、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.70、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.71、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.75;SEQ ID NO.71、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.71、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;
4种肽的组合
SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.68、SEQ ID NO.70;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQID NO.71;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.72;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.68、SEQ ID NO.73;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.69、SEQ ID NO.70;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQID NO.71;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.72;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.69、SEQ ID NO.73;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.70、SEQ ID NO.71;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.70、SEQID NO.72;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.73;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.70、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.70、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.71、SEQ ID NO.72;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.71、SEQ ID NO.73;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.71、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.71、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.72、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.68、SEQ ID NO.69、SEQ ID NO.70;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQID NO.71;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.72;SEQ ID NO.66、SEQID NO.68、SEQ ID NO.69、SEQ ID NO.73;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.68、SEQ ID NO.70、SEQ ID NO.71;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.70、SEQID NO.72;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.73;SEQ ID NO.66、SEQID NO.68、SEQ ID NO.70、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.70、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.72;SEQ ID NO.66、SEQID NO.68、SEQ ID NO.71、SEQ ID NO.73;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.71、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.68、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.72、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.68、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.71;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.72;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.73;SEQ ID NO.66、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72;SEQ ID NO.66、SEQID NO.69、SEQ ID NO.71、SEQ ID NO.73;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.71、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.69、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.69、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.72;SEQ ID NO.66、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.73;SEQ ID NO.66、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.74;SEQ ID NO.66、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.70、SEQ ID NO.72、SEQID NO.73;SEQ ID NO.66、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.66、SEQID NO.70、SEQ ID NO.72、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.70、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.70、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.70、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.73;SEQ ID NO.66、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.66、SEQID NO.71、SEQ ID NO.72、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.71、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70;SEQ ID NO.67、SEQID NO.68、SEQ ID NO.69、SEQ ID NO.71;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQID NO.72;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.73;SEQ ID NO.67、SEQID NO.68、SEQ ID NO.69、SEQ ID NO.74;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71;SEQ ID NO.67、SEQID NO.68、SEQ ID NO.70、SEQ ID NO.72;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQID NO.73;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.74;SEQ ID NO.67、SEQID NO.68、SEQ ID NO.70、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.71、SEQID NO.72;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.73;SEQ ID NO.67、SEQID NO.68、SEQ ID NO.71、SEQ ID NO.74;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.71、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.67、SEQID NO.68、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.72、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.67、SEQID NO.68、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71;SEQ ID NO.67、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.72;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.73;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.74;SEQ ID NO.67、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.71、SEQID NO.72;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.73;SEQ ID NO.67、SEQID NO.69、SEQ ID NO.71、SEQ ID NO.74;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.71、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.67、SEQID NO.69、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.72、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.67、SEQID NO.69、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72;SEQ ID NO.67、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.73;SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.75;SEQ ID NO.67、SEQID NO.70、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.75;SEQ ID NO.67、SEQID NO.70、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQID NO.71、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.67、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.75;SEQ ID NO.67、SEQID NO.71、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.67、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.71、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.67、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.71;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72;SEQ ID NO.68、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.73;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.74;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.75;SEQ ID NO.68、SEQID NO.69、SEQ ID NO.71、SEQ ID NO.72;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQID NO.73;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.74;SEQ ID NO.68、SEQID NO.69、SEQ ID NO.71、SEQ ID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.72、SEQID NO.73;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.68、SEQID NO.69、SEQ ID NO.72、SEQ ID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.68、SEQID NO.69、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.72;SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73;SEQ ID NO.68、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.74;SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.68、SEQID NO.70、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.72、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.68、SEQID NO.70、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.68、SEQID NO.71、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.68、SEQID NO.71、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.68、SEQID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.68、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.69、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.72;SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.73;SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.74;SEQ ID NO.69、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.75;SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQID NO.73;SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.69、SEQID NO.70、SEQ ID NO.72、SEQ ID NO.75;SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.69、SEQID NO.70、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.73;SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.69、SEQID NO.71、SEQ ID NO.72、SEQ ID NO.75;SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.69、SEQID NO.71、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.69、SEQID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.69、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.70、SEQID NO.71、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.75;SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.70、SEQID NO.71、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.70、SEQID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.70、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.71、SEQID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.71、SEQID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;
5种肽的组合
SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.74;SEQID NO.66、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.68、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.66、SEQ ID NO.68、SEQID NO.70、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.70、SEQID NO.72、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.73、SEQ ID NO.75;SEQID NO.66、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.68、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.66、SEQ ID NO.68、SEQID NO.71、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.71、SEQID NO.72、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.75;SEQID NO.66、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.68、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.72、SEQID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72;SEQID NO.66、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73;SEQ ID NO.66、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.69、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.72、SEQ ID NO.73;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.75;SEQID NO.66、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.66、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.69、SEQID NO.70、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.71、SEQID NO.72、SEQ ID NO.73;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.75;SEQID NO.66、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.66、SEQID NO.69、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.69、SEQID NO.71、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.72、SEQID NO.73、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQID NO.66、SEQ ID NO.69、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.66、SEQ ID NO.70、SEQID NO.71、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.72、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.75;SEQID NO.66、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.70、SEQID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.70、SEQ ID NO.72、SEQID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.70、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQID NO.66、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.71、SEQID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.71;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72;SEQID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.73;SEQ ID NO.67、SEQID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.74;SEQ ID NO.67、SEQ ID NO.68、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQID NO.71、SEQ ID NO.72;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQID NO.73;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.74;SEQID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.75;SEQ ID NO.67、SEQID NO.68、SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.67、SEQ ID NO.68、SEQID NO.69、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQID NO.72、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.73、SEQ ID NO.75;SEQID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72;SEQ ID NO.67、SEQ ID NO.68、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.73;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQID NO.71、SEQ ID NO.74;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73;SEQID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.67、SEQID NO.68、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQID NO.70、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQID NO.73、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73;SEQID NO.67、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.67、SEQID NO.68、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQID NO.71、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.71、SEQID NO.73、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQID NO.67、SEQ ID NO.68、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.67、SEQID NO.68、SEQ ID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.71、SEQ ID NO.72;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.73;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.74;SEQID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.75;SEQ ID NO.67、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.67、SEQ ID NO.69、SEQID NO.70、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.72、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.73、SEQ ID NO.75;SEQID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.67、SEQ ID NO.69、SEQID NO.71、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.71、SEQID NO.72、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.75;SEQID NO.67、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQID NO.69、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.67、SEQ ID NO.69、SEQID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.72、SEQID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73;SEQID NO.67、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.67、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.70、SEQID NO.71、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.73、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQID NO.67、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.67、SEQID NO.70、SEQ ID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.70、SEQID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.73、SEQ ID NO.74;SEQ ID NO.67、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQID NO.67、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.72;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.71、SEQ ID NO.73;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.74;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.75;SEQID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.68、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.68、SEQ ID NO.69、SEQID NO.70、SEQ ID NO.72、SEQ ID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.73、SEQ ID NO.74;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.74、SEQ ID NO.75;SEQID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.68、SEQID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.68、SEQ ID NO.69、SEQID NO.71、SEQ ID NO.72、SEQ ID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQID NO.73、SEQ ID NO.74;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.74、SEQ ID NO.75;SEQID NO.68、SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.68、SEQID NO.69、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.73、SEQID NO.74、SEQ ID NO.75;SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.73;SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74;SEQID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.75;SEQ ID NO.68、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.68、SEQ ID NO.70、SEQID NO.71、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.74、SEQ ID NO.75;SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQID NO.68、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.68、SEQID NO.70、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.68、SEQ ID NO.71、SEQID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.73、SEQ ID NO.75;SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQID NO.68、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.69、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.69、SEQ ID NO.70、SEQID NO.71、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.72、SEQ ID NO.75;SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.75;SEQID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.69、SEQID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.69、SEQ ID NO.70、SEQID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQID NO.74、SEQ ID NO.75;SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.69、SEQID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.69、SEQ ID NO.71、SEQID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74、SEQ ID NO.75;SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.70、SEQID NO.71、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.70、SEQ ID NO.72、SEQID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74、SEQ ID NO.75;
6种肽的组合
SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.71;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.72;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.73;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQID NO.72;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQID NO.73;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.72、SEQID NO.73;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.72、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.72;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.73;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.72、SEQID NO.73;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.72、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.73;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.72;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.73;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQID NO.73;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.73;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.73;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.72;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.73;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQID NO.73;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.73;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.73;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.73;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.72;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.73;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQID NO.73;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.73;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.73;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.73;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.73;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;
7种肽的组合
SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.71、SEQ ID NO.72;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.73;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73;SEQID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.72、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQID NO.70、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73;SEQID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQID NO.72、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQID NO.71、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQID NO.69、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.72、SEQID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.66、SEQ ID NO.67、SEQID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.75;SEQID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQID NO.71、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQID NO.68、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.73、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.71、SEQID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQID NO.68、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.68、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.73;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.72、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.71、SEQ ID NO.72、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.74、SEQ ID NO.75;SEQID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQID NO.70、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.72、SEQID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.70、SEQID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQID NO.66、SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.66、SEQ ID NO.68、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.66、SEQID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.75;SEQID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.71、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.73、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQID NO.69、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.68、SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQID NO.66、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.70、SEQID NO.71、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.68、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQID NO.66、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.74;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.71、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.69、SEQID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQID NO.66、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.72、SEQ ID NO.73;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.71、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.67、SEQID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.75;SEQID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQID NO.73、SEQ ID NO.74;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQID NO.70、SEQ ID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.67、SEQID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.72、SEQID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.71、SEQID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.67、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.71、SEQID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.70、SEQID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.68、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.74、SEQ ID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.68、SEQ ID NO.69、SEQID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.68、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;
8种肽的组合
SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.71、SEQ ID NO.72、SEQ ID NO.73;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.71、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQID NO.69、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.68、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.69、SEQID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.67、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.66、SEQID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.70、SEQID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.75;SEQ ID NO.67、SEQID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQID NO.70、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.68、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;
9种肽的组合
SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74;SEQ ID NO.66、SEQ ID NO.67、SEQID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.71、SEQ ID NO.72、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQID NO.68、SEQ ID NO.69、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQ ID NO.68、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.66、SEQ ID NO.67、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;SEQ ID NO.66、SEQ ID NO.68、SEQ ID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQ ID NO.75;SEQ ID NO.67、SEQ ID NO.68、SEQID NO.69、SEQ ID NO.70、SEQ ID NO.71、SEQ ID NO.72、SEQ ID NO.73、SEQ ID NO.74、SEQID NO.75;
表6.来自表5的氨基酸序列的组合,待掺入免疫原性肽中,用于组成根据本发明的合成长肽的组合物。各种组合通过分号分开。
2种肽的组合
SEQ ID NO.76、SEQ ID NO.77;SEQ ID NO.76、SEQ ID NO.78;SEQ ID NO.76、SEQID NO.79;SEQ ID NO.76、SEQ ID NO.80;SEQ ID NO.76、SEQ ID NO.81;SEQ ID NO.76、SEQID NO.82;SEQ ID NO.76、SEQ ID NO.83;SEQ ID NO.76、SEQ ID NO.84;SEQ ID NO.76、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78;SEQ ID NO.77、SEQ ID NO.79;SEQ ID NO.77、SEQID NO.80;SEQ ID NO.77、SEQ ID NO.81;SEQ ID NO.77、SEQ ID NO.82;SEQ ID NO.77、SEQID NO.83;SEQ ID NO.77、SEQ ID NO.84;SEQ ID NO.77、SEQ ID NO.85;SEQ ID NO.78、SEQID NO.79;SEQ ID NO.78、SEQ ID NO.80;SEQ ID NO.78、SEQ ID NO.81;SEQ ID NO.78、SEQID NO.82;SEQ ID NO.78、SEQ ID NO.83;SEQ ID NO.78、SEQ ID NO.84;SEQ ID NO.78、SEQID NO.85;SEQ ID NO.79、SEQ ID NO.80;SEQ ID NO.79、SEQ ID NO.81;SEQ ID NO.79、SEQID NO.82;SEQ ID NO.79、SEQ ID NO.83;SEQ ID NO.79、SEQ ID NO.84;SEQ ID NO.79、SEQID NO.85;SEQ ID NO.80、SEQ ID NO.81;SEQ ID NO.80、SEQ ID NO.82;SEQ ID NO.80、SEQID NO.83;SEQ ID NO.80、SEQ ID NO.84;SEQ ID NO.80、SEQ ID NO.85;SEQ ID NO.81、SEQID NO.82;SEQ ID NO.81、SEQ ID NO.83;SEQ ID NO.81、SEQ ID NO.84;SEQ ID NO.81、SEQID NO.85;SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.82、SEQID NO.85;SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.84、SEQID NO.85;
3种肽的组合
SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78;SEQ ID NO.76、SEQ ID NO.77、SEQID NO.79;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.80;SEQ ID NO.76、SEQ ID NO.77、SEQID NO.81;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.82;SEQ ID NO.76、SEQ ID NO.77、SEQID NO.83;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79;SEQ ID NO.76、SEQ ID NO.78、SEQID NO.80;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.81;SEQ ID NO.76、SEQ ID NO.78、SEQID NO.82;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.83;SEQ ID NO.76、SEQ ID NO.78、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.79、SEQID NO.80;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.81;SEQ ID NO.76、SEQ ID NO.79、SEQID NO.82;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.83;SEQ ID NO.76、SEQ ID NO.79、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.80、SEQID NO.81;SEQ ID NO.76、SEQ ID NO.80、SEQ ID NO.82;SEQ ID NO.76、SEQ ID NO.80、SEQID NO.83;SEQ ID NO.76、SEQ ID NO.80、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.80、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.81、SEQ ID NO.82;SEQ ID NO.76、SEQ ID NO.81、SEQID NO.83;SEQ ID NO.76、SEQ ID NO.81、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.81、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.76、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.82、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79;SEQ ID NO.77、SEQ ID NO.78、SEQID NO.80;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.81;SEQ ID NO.77、SEQ ID NO.78、SEQID NO.82;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.83;SEQ ID NO.77、SEQ ID NO.78、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQID NO.80;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.81;SEQ ID NO.77、SEQ ID NO.79、SEQID NO.82;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.83;SEQ ID NO.77、SEQ ID NO.79、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.80、SEQID NO.81;SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.82;SEQ ID NO.77、SEQ ID NO.80、SEQID NO.83;SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.84;SEQ ID NO.77、SEQ ID NO.80、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.81、SEQ ID NO.82;SEQ ID NO.77、SEQ ID NO.81、SEQID NO.83;SEQ ID NO.77、SEQ ID NO.81、SEQ ID NO.84;SEQ ID NO.77、SEQ ID NO.81、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.77、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.82、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80;SEQ ID NO.78、SEQ ID NO.79、SEQID NO.81;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.82;SEQ ID NO.78、SEQ ID NO.79、SEQID NO.83;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.84;SEQ ID NO.78、SEQ ID NO.79、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81;SEQ ID NO.78、SEQ ID NO.80、SEQID NO.82;SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.83;SEQ ID NO.78、SEQ ID NO.80、SEQID NO.84;SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.85;SEQ ID NO.78、SEQ ID NO.81、SEQID NO.82;SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.83;SEQ ID NO.78、SEQ ID NO.81、SEQID NO.84;SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.85;SEQ ID NO.78、SEQ ID NO.82、SEQID NO.83;SEQ ID NO.78、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.78、SEQ ID NO.82、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.78、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.79、SEQ ID NO.80、SEQID NO.81;SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82;SEQ ID NO.79、SEQ ID NO.80、SEQID NO.83;SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.84;SEQ ID NO.79、SEQ ID NO.80、SEQID NO.85;SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82;SEQ ID NO.79、SEQ ID NO.81、SEQID NO.83;SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.84;SEQ ID NO.79、SEQ ID NO.81、SEQID NO.85;SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.79、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.85;SEQ ID NO.79、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.79、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.79、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82;SEQ ID NO.80、SEQ ID NO.81、SEQID NO.83;SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.84;SEQ ID NO.80、SEQ ID NO.81、SEQID NO.85;SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.80、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.85;SEQ ID NO.80、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.80、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.80、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.81、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.85;SEQ ID NO.81、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.81、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;
4种肽的组合
SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.78、SEQ ID NO.80;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQID NO.81;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.82;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.78、SEQ ID NO.83;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.79、SEQ ID NO.80;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQID NO.81;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.82;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.79、SEQ ID NO.83;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.80、SEQ ID NO.81;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.80、SEQID NO.82;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.83;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.80、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.80、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.81、SEQ ID NO.82;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.81、SEQ ID NO.83;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.81、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.81、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.82、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.78、SEQ ID NO.79、SEQ ID NO.80;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQID NO.81;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.82;SEQ ID NO.76、SEQID NO.78、SEQ ID NO.79、SEQ ID NO.83;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.78、SEQ ID NO.80、SEQ ID NO.81;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.80、SEQID NO.82;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.83;SEQ ID NO.76、SEQID NO.78、SEQ ID NO.80、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.80、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.82;SEQ ID NO.76、SEQID NO.78、SEQ ID NO.81、SEQ ID NO.83;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.81、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.78、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.82、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.78、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.81;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.82;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.83;SEQ ID NO.76、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82;SEQ ID NO.76、SEQID NO.79、SEQ ID NO.81、SEQ ID NO.83;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.81、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.79、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.79、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.82;SEQ ID NO.76、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.83;SEQ ID NO.76、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.84;SEQ ID NO.76、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.80、SEQ ID NO.82、SEQID NO.83;SEQ ID NO.76、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.76、SEQID NO.80、SEQ ID NO.82、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.80、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.80、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.80、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.83;SEQ ID NO.76、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.76、SEQID NO.81、SEQ ID NO.82、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.81、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80;SEQ ID NO.77、SEQID NO.78、SEQ ID NO.79、SEQ ID NO.81;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQID NO.82;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.83;SEQ ID NO.77、SEQID NO.78、SEQ ID NO.79、SEQ ID NO.84;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81;SEQ ID NO.77、SEQID NO.78、SEQ ID NO.80、SEQ ID NO.82;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQID NO.83;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.84;SEQ ID NO.77、SEQID NO.78、SEQ ID NO.80、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.81、SEQID NO.82;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.83;SEQ ID NO.77、SEQID NO.78、SEQ ID NO.81、SEQ ID NO.84;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.81、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.77、SEQID NO.78、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.82、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.77、SEQID NO.78、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81;SEQ ID NO.77、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.82;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.83;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.84;SEQ ID NO.77、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.81、SEQID NO.82;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.83;SEQ ID NO.77、SEQID NO.79、SEQ ID NO.81、SEQ ID NO.84;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.81、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.77、SEQID NO.79、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.82、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.77、SEQID NO.79、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82;SEQ ID NO.77、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.83;SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.85;SEQ ID NO.77、SEQID NO.80、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.85;SEQ ID NO.77、SEQID NO.80、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQID NO.81、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.77、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.85;SEQ ID NO.77、SEQID NO.81、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.77、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.81、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.77、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.81;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82;SEQ ID NO.78、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.83;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.84;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.85;SEQ ID NO.78、SEQID NO.79、SEQ ID NO.81、SEQ ID NO.82;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQID NO.83;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.84;SEQ ID NO.78、SEQID NO.79、SEQ ID NO.81、SEQ ID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.82、SEQID NO.83;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.78、SEQID NO.79、SEQ ID NO.82、SEQ ID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.78、SEQID NO.79、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.82;SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83;SEQ ID NO.78、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.84;SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.78、SEQID NO.80、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.82、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.78、SEQID NO.80、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.78、SEQID NO.81、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.78、SEQID NO.81、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.78、SEQID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.78、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.79、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.82;SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.83;SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.84;SEQ ID NO.79、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.85;SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQID NO.83;SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.79、SEQID NO.80、SEQ ID NO.82、SEQ ID NO.85;SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.79、SEQID NO.80、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.83;SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.79、SEQID NO.81、SEQ ID NO.82、SEQ ID NO.85;SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.79、SEQID NO.81、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.79、SEQID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.79、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.80、SEQID NO.81、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.85;SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.80、SEQID NO.81、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.80、SEQID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.80、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.81、SEQID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.81、SEQID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;
5种肽的组合
SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.84;SEQID NO.76、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.78、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.76、SEQ ID NO.78、SEQID NO.80、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.80、SEQID NO.82、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.83、SEQ ID NO.85;SEQID NO.76、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.78、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.76、SEQ ID NO.78、SEQID NO.81、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.81、SEQID NO.82、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.85;SEQID NO.76、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.78、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.82、SEQID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82;SEQID NO.76、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83;SEQ ID NO.76、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.79、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.82、SEQ ID NO.83;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.85;SEQID NO.76、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.76、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.79、SEQID NO.80、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.81、SEQID NO.82、SEQ ID NO.83;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.85;SEQID NO.76、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.76、SEQID NO.79、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.79、SEQID NO.81、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.82、SEQID NO.83、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQID NO.76、SEQ ID NO.79、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.76、SEQ ID NO.80、SEQID NO.81、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.82、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.85;SEQID NO.76、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.80、SEQID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.80、SEQ ID NO.82、SEQID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.80、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQID NO.76、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.81、SEQID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.81;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82;SEQID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.83;SEQ ID NO.77、SEQID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.84;SEQ ID NO.77、SEQ ID NO.78、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQID NO.81、SEQ ID NO.82;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQID NO.83;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.84;SEQID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.85;SEQ ID NO.77、SEQID NO.78、SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.77、SEQ ID NO.78、SEQID NO.79、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQID NO.82、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.83、SEQ ID NO.85;SEQID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82;SEQ ID NO.77、SEQ ID NO.78、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.83;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQID NO.81、SEQ ID NO.84;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83;SEQID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.77、SEQID NO.78、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQID NO.80、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQID NO.83、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83;SEQID NO.77、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.77、SEQID NO.78、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQID NO.81、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.81、SEQID NO.83、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQID NO.77、SEQ ID NO.78、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.77、SEQID NO.78、SEQ ID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.81、SEQ ID NO.82;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.83;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.84;SEQID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.85;SEQ ID NO.77、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.77、SEQ ID NO.79、SEQID NO.80、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.82、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.83、SEQ ID NO.85;SEQID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.77、SEQ ID NO.79、SEQID NO.81、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.81、SEQID NO.82、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.85;SEQID NO.77、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQID NO.79、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.77、SEQ ID NO.79、SEQID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.82、SEQID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83;SEQID NO.77、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.77、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.80、SEQID NO.81、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.83、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQID NO.77、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.77、SEQID NO.80、SEQ ID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.80、SEQID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.83、SEQ ID NO.84;SEQ ID NO.77、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQID NO.77、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.82;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.81、SEQ ID NO.83;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.84;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.85;SEQID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.78、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.78、SEQ ID NO.79、SEQID NO.80、SEQ ID NO.82、SEQ ID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.83、SEQ ID NO.84;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.84、SEQ ID NO.85;SEQID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.78、SEQID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.78、SEQ ID NO.79、SEQID NO.81、SEQ ID NO.82、SEQ ID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQID NO.83、SEQ ID NO.84;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.84、SEQ ID NO.85;SEQID NO.78、SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.78、SEQID NO.79、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.83、SEQID NO.84、SEQ ID NO.85;SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.83;SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84;SEQID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.85;SEQ ID NO.78、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.78、SEQ ID NO.80、SEQID NO.81、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.84、SEQ ID NO.85;SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQID NO.78、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.78、SEQID NO.80、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.78、SEQ ID NO.81、SEQID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.83、SEQ ID NO.85;SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQID NO.78、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.79、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.79、SEQ ID NO.80、SEQID NO.81、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.82、SEQ ID NO.85;SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.85;SEQID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.79、SEQID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.79、SEQ ID NO.80、SEQID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQID NO.84、SEQ ID NO.85;SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.79、SEQID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.79、SEQ ID NO.81、SEQID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84、SEQ ID NO.85;SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.80、SEQID NO.81、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.80、SEQ ID NO.82、SEQID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84、SEQ ID NO.85;
6种肽的组合
SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.81;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.82;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.83;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQID NO.82;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQID NO.83;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.82、SEQID NO.83;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.82、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.82;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.83;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.82、SEQID NO.83;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.82、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.83;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.82;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.83;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQID NO.83;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.83;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.83;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.82;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.83;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQID NO.83;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.83;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.83;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.83;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.82;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.83;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQID NO.83;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.83;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.83;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.83;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.83;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;
7种肽的组合
SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.81、SEQ ID NO.82;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.83;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83;SEQID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.82、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQID NO.80、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83;SEQID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQID NO.82、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQID NO.81、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQID NO.79、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.82、SEQID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.76、SEQ ID NO.77、SEQID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.85;SEQID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQID NO.81、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQID NO.78、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.83、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.81、SEQID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQID NO.78、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.78、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.83;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.82、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.81、SEQ ID NO.82、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.84、SEQ ID NO.85;SEQID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQID NO.80、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.82、SEQID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.80、SEQID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQID NO.76、SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.76、SEQ ID NO.78、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.76、SEQID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.85;SEQID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.81、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.83、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQID NO.79、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.78、SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQID NO.76、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.80、SEQID NO.81、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.78、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQID NO.76、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.84;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.81、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.79、SEQID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQID NO.76、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.82、SEQ ID NO.83;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.81、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.77、SEQID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.85;SEQID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQID NO.83、SEQ ID NO.84;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQID NO.80、SEQ ID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.77、SEQID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.82、SEQID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.81、SEQID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.77、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.81、SEQID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.80、SEQID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.78、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.84、SEQ ID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.78、SEQ ID NO.79、SEQID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.78、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;
8种肽的组合
SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.81、SEQ ID NO.82、SEQ ID NO.83;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.81、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQID NO.79、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.78、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.79、SEQID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.77、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.76、SEQID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.80、SEQID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.85;SEQ ID NO.77、SEQID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQID NO.80、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.78、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;
9种肽的组合
SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84;SEQ ID NO.76、SEQ ID NO.77、SEQID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.81、SEQ ID NO.82、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQID NO.78、SEQ ID NO.79、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQ ID NO.78、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.76、SEQ ID NO.77、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85;SEQ ID NO.76、SEQ ID NO.78、SEQ ID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQ ID NO.85;SEQ ID NO.77、SEQ ID NO.78、SEQID NO.79、SEQ ID NO.80、SEQ ID NO.81、SEQ ID NO.82、SEQ ID NO.83、SEQ ID NO.84、SEQID NO.85。
序列表
<110> 潘塔希生物科学股份有限公司
<120> 用于治疗和/或预防肺癌的免疫治疗方法
<130> P6066722PCT
<150> EP17199441.1
<151> 2017-10-31
<160> 85
<170> PatentIn version 3.5
<210> 1
<211> 638
<212> PRT
<213> 智人
<400> 1
Met Ala Gly Gly Ser Ala Thr Thr Trp Gly Tyr Pro Val Ala Leu Leu
1 5 10 15
Leu Leu Val Ala Thr Leu Gly Leu Gly Arg Trp Leu Gln Pro Asp Pro
20 25 30
Gly Leu Pro Gly Leu Arg His Ser Tyr Asp Cys Gly Ile Lys Gly Met
35 40 45
Gln Leu Leu Val Phe Pro Arg Pro Gly Gln Thr Leu Arg Phe Lys Val
50 55 60
Val Asp Glu Phe Gly Asn Arg Phe Asp Val Asn Asn Cys Ser Ile Cys
65 70 75 80
Tyr His Trp Val Thr Ser Arg Pro Gln Glu Pro Ala Val Phe Ser Ala
85 90 95
Asp Tyr Arg Gly Cys His Val Leu Glu Lys Asp Gly Arg Phe His Leu
100 105 110
Arg Val Phe Met Glu Ala Val Leu Pro Asn Gly Arg Val Asp Val Ala
115 120 125
Gln Asp Ala Thr Leu Ile Cys Pro Lys Pro Asp Pro Ser Arg Thr Leu
130 135 140
Asp Ser Gln Leu Ala Pro Pro Ala Met Phe Ser Val Ser Thr Pro Gln
145 150 155 160
Thr Leu Ser Phe Leu Pro Thr Ser Gly His Thr Ser Gln Gly Ser Gly
165 170 175
His Ala Phe Pro Ser Pro Leu Asp Pro Gly His Ser Ser Val His Pro
180 185 190
Thr Pro Ala Leu Pro Ser Pro Gly Pro Gly Pro Thr Leu Ala Thr Leu
195 200 205
Ala Gln Pro His Trp Gly Thr Leu Glu His Trp Asp Val Asn Lys Arg
210 215 220
Asp Tyr Ile Gly Thr His Leu Ser Gln Glu Gln Cys Gln Val Ala Ser
225 230 235 240
Gly His Leu Pro Cys Ile Val Arg Arg Thr Ser Lys Glu Ala Cys Gln
245 250 255
Gln Ala Gly Cys Cys Tyr Asp Asn Thr Arg Glu Val Pro Cys Tyr Tyr
260 265 270
Gly Asn Thr Ala Thr Val Gln Cys Phe Arg Asp Gly Tyr Phe Val Leu
275 280 285
Val Val Ser Gln Glu Met Ala Leu Thr His Arg Ile Thr Leu Ala Asn
290 295 300
Ile His Leu Ala Tyr Ala Pro Thr Ser Cys Ser Pro Thr Gln His Thr
305 310 315 320
Glu Ala Phe Val Val Phe Tyr Phe Pro Leu Thr His Cys Gly Thr Thr
325 330 335
Met Gln Val Ala Gly Asp Gln Leu Ile Tyr Glu Asn Trp Leu Val Ser
340 345 350
Gly Ile His Ile Gln Lys Gly Pro Gln Gly Ser Ile Thr Arg Asp Ser
355 360 365
Thr Phe Gln Leu His Val Arg Cys Val Phe Asn Ala Ser Asp Phe Leu
370 375 380
Pro Ile Gln Ala Ser Ile Phe Pro Pro Pro Ser Pro Ala Pro Met Thr
385 390 395 400
Gln Pro Gly Pro Leu Arg Leu Glu Leu Arg Ile Ala Lys Asp Glu Thr
405 410 415
Phe Ser Ser Tyr Tyr Gly Glu Asp Asp Tyr Pro Ile Val Arg Leu Leu
420 425 430
Arg Glu Pro Val His Val Glu Val Arg Leu Leu Gln Arg Thr Asp Pro
435 440 445
Asn Leu Val Leu Leu Leu His Gln Cys Trp Gly Ala Pro Ser Ala Asn
450 455 460
Pro Phe Gln Gln Pro Gln Trp Pro Ile Leu Ser Asp Gly Cys Pro Phe
465 470 475 480
Lys Gly Asp Ser Tyr Arg Thr Gln Met Val Ala Leu Asp Gly Ala Thr
485 490 495
Pro Phe Gln Ser His Tyr Gln Arg Phe Thr Val Ala Thr Phe Ala Leu
500 505 510
Leu Asp Ser Gly Ser Gln Arg Ala Leu Arg Gly Leu Val Tyr Leu Phe
515 520 525
Cys Ser Thr Ser Ala Cys His Thr Ser Gly Leu Glu Thr Cys Ser Thr
530 535 540
Ala Cys Ser Thr Gly Thr Thr Arg Gln Arg Arg Ser Ser Gly His Arg
545 550 555 560
Asn Asp Thr Ala Arg Pro Gln Asp Ile Val Ser Ser Pro Gly Pro Val
565 570 575
Gly Phe Glu Asp Ser Tyr Gly Gln Glu Pro Thr Leu Gly Pro Thr Asp
580 585 590
Ser Asn Gly Asn Ser Ser Leu Arg Pro Leu Leu Trp Ala Val Leu Leu
595 600 605
Leu Pro Ala Val Ala Leu Val Leu Gly Phe Gly Val Phe Val Gly Leu
610 615 620
Ser Gln Thr Trp Ala Gln Lys Leu Trp Glu Ser Asn Arg Gln
625 630 635
<210> 2
<211> 745
<212> PRT
<213> 智人
<400> 2
Met Ala Cys Arg Gln Arg Gly Gly Ser Trp Ser Pro Ser Gly Trp Phe
1 5 10 15
Asn Ala Gly Trp Ser Thr Tyr Arg Ser Ile Ser Leu Phe Phe Ala Leu
20 25 30
Val Thr Ser Gly Asn Ser Ile Asp Val Ser Gln Leu Val Asn Pro Ala
35 40 45
Phe Pro Gly Thr Val Thr Cys Asp Glu Arg Glu Ile Thr Val Glu Phe
50 55 60
Pro Ser Ser Pro Gly Thr Lys Lys Trp His Ala Ser Val Val Asp Pro
65 70 75 80
Leu Gly Leu Asp Met Pro Asn Cys Thr Tyr Ile Leu Asp Pro Glu Lys
85 90 95
Leu Thr Leu Arg Ala Thr Tyr Asp Asn Cys Thr Arg Arg Val His Gly
100 105 110
Gly His Gln Met Thr Ile Arg Val Met Asn Asn Ser Ala Ala Leu Arg
115 120 125
His Gly Ala Val Met Tyr Gln Phe Phe Cys Pro Ala Met Gln Val Glu
130 135 140
Glu Thr Gln Gly Leu Ser Ala Ser Thr Ile Cys Gln Lys Asp Phe Met
145 150 155 160
Ser Phe Ser Leu Pro Arg Val Phe Ser Gly Leu Ala Asp Asp Ser Lys
165 170 175
Gly Thr Lys Val Gln Met Gly Trp Ser Ile Glu Val Gly Asp Gly Ala
180 185 190
Arg Ala Lys Thr Leu Thr Leu Pro Glu Ala Met Lys Glu Gly Phe Ser
195 200 205
Leu Leu Ile Asp Asn His Arg Met Thr Phe His Val Pro Phe Asn Ala
210 215 220
Thr Gly Val Thr His Tyr Val Gln Gly Asn Ser His Leu Tyr Met Val
225 230 235 240
Ser Leu Lys Leu Thr Phe Ile Ser Pro Gly Gln Lys Val Ile Phe Ser
245 250 255
Ser Gln Ala Ile Cys Ala Pro Asp Pro Val Thr Cys Asn Ala Thr His
260 265 270
Met Thr Leu Thr Ile Pro Glu Phe Pro Gly Lys Leu Lys Ser Val Ser
275 280 285
Phe Glu Asn Gln Asn Ile Asp Val Ser Gln Leu His Asp Asn Gly Ile
290 295 300
Asp Leu Glu Ala Thr Asn Gly Met Lys Leu His Phe Ser Lys Thr Leu
305 310 315 320
Leu Lys Thr Lys Leu Ser Glu Lys Cys Leu Leu His Gln Phe Tyr Leu
325 330 335
Ala Ser Leu Lys Leu Thr Phe Leu Leu Arg Pro Glu Thr Val Ser Met
340 345 350
Val Ile Tyr Pro Glu Cys Leu Cys Glu Ser Pro Val Ser Ile Val Thr
355 360 365
Gly Glu Leu Cys Thr Gln Asp Gly Phe Met Asp Val Glu Val Tyr Ser
370 375 380
Tyr Gln Thr Gln Pro Ala Leu Asp Leu Gly Thr Leu Arg Val Gly Asn
385 390 395 400
Ser Ser Cys Gln Pro Val Phe Glu Ala Gln Ser Gln Gly Leu Val Arg
405 410 415
Phe His Ile Pro Leu Asn Gly Cys Gly Thr Arg Tyr Lys Phe Glu Asp
420 425 430
Asp Lys Val Val Tyr Glu Asn Glu Ile His Ala Leu Trp Thr Asp Phe
435 440 445
Pro Pro Ser Lys Ile Ser Arg Asp Ser Glu Phe Arg Met Thr Val Lys
450 455 460
Cys Ser Tyr Ser Arg Asn Asp Met Leu Leu Asn Ile Asn Val Glu Ser
465 470 475 480
Leu Thr Pro Pro Val Ala Ser Val Lys Leu Gly Pro Phe Thr Leu Ile
485 490 495
Leu Gln Ser Tyr Pro Asp Asn Ser Tyr Gln Gln Pro Tyr Gly Glu Asn
500 505 510
Glu Tyr Pro Leu Val Arg Phe Leu Arg Gln Pro Ile Tyr Met Glu Val
515 520 525
Arg Val Leu Asn Arg Asp Asp Pro Asn Ile Lys Leu Val Leu Asp Asp
530 535 540
Cys Trp Ala Thr Ser Thr Met Asp Pro Asp Ser Phe Pro Gln Trp Asn
545 550 555 560
Val Val Val Asp Gly Cys Ala Tyr Asp Leu Asp Asn Tyr Gln Thr Thr
565 570 575
Phe His Pro Val Gly Ser Ser Val Thr His Pro Asp His Tyr Gln Arg
580 585 590
Phe Asp Met Lys Ala Phe Ala Phe Val Ser Glu Ala His Val Leu Ser
595 600 605
Ser Leu Val Tyr Phe His Cys Ser Ala Leu Ile Cys Asn Arg Leu Ser
610 615 620
Pro Asp Ser Pro Leu Cys Ser Val Thr Cys Pro Val Ser Ser Arg His
625 630 635 640
Arg Arg Ala Thr Gly Ala Thr Glu Ala Glu Lys Met Thr Val Ser Leu
645 650 655
Pro Gly Pro Ile Leu Leu Leu Ser Asp Asp Ser Ser Phe Arg Gly Val
660 665 670
Gly Ser Ser Asp Leu Lys Ala Ser Gly Ser Ser Gly Glu Lys Ser Arg
675 680 685
Ser Glu Thr Gly Glu Glu Val Gly Ser Arg Gly Ala Met Asp Thr Lys
690 695 700
Gly His Lys Thr Ala Gly Asp Val Gly Ser Lys Ala Val Ala Ala Val
705 710 715 720
Ala Ala Phe Ala Gly Val Val Ala Thr Leu Gly Phe Ile Tyr Tyr Leu
725 730 735
Tyr Glu Lys Arg Thr Val Ser Asn His
740 745
<210> 3
<211> 424
<212> PRT
<213> 智人
<400> 3
Met Glu Leu Ser Tyr Arg Leu Phe Ile Cys Leu Leu Leu Trp Gly Ser
1 5 10 15
Thr Glu Leu Cys Tyr Pro Gln Pro Leu Trp Leu Leu Gln Gly Gly Ala
20 25 30
Ser His Pro Glu Thr Ser Val Gln Pro Val Leu Val Glu Cys Gln Glu
35 40 45
Ala Thr Leu Met Val Met Val Ser Lys Asp Leu Phe Gly Thr Gly Lys
50 55 60
Leu Ile Arg Ala Ala Asp Leu Thr Leu Gly Pro Glu Ala Cys Glu Pro
65 70 75 80
Leu Val Ser Met Asp Thr Glu Asp Val Val Arg Phe Glu Val Gly Leu
85 90 95
His Glu Cys Gly Asn Ser Met Gln Val Thr Asp Asp Ala Leu Val Tyr
100 105 110
Ser Thr Phe Leu Leu His Asp Pro Arg Pro Val Gly Asn Leu Ser Ile
115 120 125
Val Arg Thr Asn Arg Ala Glu Ile Pro Ile Glu Cys Arg Tyr Pro Arg
130 135 140
Gln Gly Asn Val Ser Ser Gln Ala Ile Leu Pro Thr Trp Leu Pro Phe
145 150 155 160
Arg Thr Thr Val Phe Ser Glu Glu Lys Leu Thr Phe Ser Leu Arg Leu
165 170 175
Met Glu Glu Asn Trp Asn Ala Glu Lys Arg Ser Pro Thr Phe His Leu
180 185 190
Gly Asp Ala Ala His Leu Gln Ala Glu Ile His Thr Gly Ser His Val
195 200 205
Pro Leu Arg Leu Phe Val Asp His Cys Val Ala Thr Pro Thr Pro Asp
210 215 220
Gln Asn Ala Ser Pro Tyr His Thr Ile Val Asp Phe His Gly Cys Leu
225 230 235 240
Val Asp Gly Leu Thr Asp Ala Ser Ser Ala Phe Lys Val Pro Arg Pro
245 250 255
Gly Pro Asp Thr Leu Gln Phe Thr Val Asp Val Phe His Phe Ala Asn
260 265 270
Asp Ser Arg Asn Met Ile Tyr Ile Thr Cys His Leu Lys Val Thr Leu
275 280 285
Ala Glu Gln Asp Pro Asp Glu Leu Asn Lys Ala Cys Ser Phe Ser Lys
290 295 300
Pro Ser Asn Ser Trp Phe Pro Val Glu Gly Ser Ala Asp Ile Cys Gln
305 310 315 320
Cys Cys Asn Lys Gly Asp Cys Gly Thr Pro Ser His Ser Arg Arg Gln
325 330 335
Pro His Val Met Ser Gln Trp Ser Arg Ser Ala Ser Arg Asn Arg Arg
340 345 350
His Val Thr Glu Glu Ala Asp Val Thr Val Gly Pro Leu Ile Phe Leu
355 360 365
Asp Arg Arg Gly Asp His Glu Val Glu Gln Trp Ala Leu Pro Ser Asp
370 375 380
Thr Ser Val Val Leu Leu Gly Val Gly Leu Ala Val Val Val Ser Leu
385 390 395 400
Thr Leu Thr Ala Val Ile Leu Val Leu Thr Arg Arg Cys Arg Thr Ala
405 410 415
Ser His Pro Val Ser Ala Ser Glu
420
<210> 4
<211> 540
<212> PRT
<213> 智人
<400> 4
Met Trp Leu Leu Arg Cys Val Leu Leu Cys Val Ser Leu Ser Leu Ala
1 5 10 15
Val Ser Gly Gln His Lys Pro Glu Ala Pro Asp Tyr Ser Ser Val Leu
20 25 30
His Cys Gly Pro Trp Ser Phe Gln Phe Ala Val Asn Leu Asn Gln Glu
35 40 45
Ala Thr Ser Pro Pro Val Leu Ile Ala Trp Asp Asn Gln Gly Leu Leu
50 55 60
His Glu Leu Gln Asn Asp Ser Asp Cys Gly Thr Trp Ile Arg Lys Gly
65 70 75 80
Pro Gly Ser Ser Val Val Leu Glu Ala Thr Tyr Ser Ser Cys Tyr Val
85 90 95
Thr Glu Trp Asp Ser His Tyr Ile Met Pro Val Gly Val Glu Gly Ala
100 105 110
Gly Ala Ala Glu His Lys Val Val Thr Glu Arg Lys Leu Leu Lys Cys
115 120 125
Pro Met Asp Leu Leu Ala Arg Asp Ala Pro Asp Thr Asp Trp Cys Asp
130 135 140
Ser Ile Pro Ala Arg Asp Arg Leu Pro Cys Ala Pro Ser Pro Ile Ser
145 150 155 160
Arg Gly Asp Cys Glu Gly Leu Gly Cys Cys Tyr Ser Ser Glu Glu Val
165 170 175
Asn Ser Cys Tyr Tyr Gly Asn Thr Val Thr Leu His Cys Thr Arg Glu
180 185 190
Gly His Phe Ser Ile Ala Val Ser Arg Asn Val Thr Ser Pro Pro Leu
195 200 205
Leu Leu Asp Ser Val Arg Leu Ala Leu Arg Asn Asp Ser Ala Cys Asn
210 215 220
Pro Val Met Ala Thr Gln Ala Phe Val Leu Phe Gln Phe Pro Phe Thr
225 230 235 240
Ser Cys Gly Thr Thr Arg Gln Ile Thr Gly Asp Arg Ala Val Tyr Glu
245 250 255
Asn Glu Leu Val Ala Thr Arg Asp Val Lys Asn Gly Ser Arg Gly Ser
260 265 270
Val Thr Arg Asp Ser Ile Phe Arg Leu His Val Ser Cys Ser Tyr Ser
275 280 285
Val Ser Ser Asn Ser Leu Pro Ile Asn Val Gln Val Phe Thr Leu Pro
290 295 300
Pro Pro Phe Pro Glu Thr Gln Pro Gly Pro Leu Thr Leu Glu Leu Gln
305 310 315 320
Ile Ala Lys Asp Lys Asn Tyr Gly Ser Tyr Tyr Gly Val Gly Asp Tyr
325 330 335
Pro Val Val Lys Leu Leu Arg Asp Pro Ile Tyr Val Glu Val Ser Ile
340 345 350
Leu His Arg Thr Asp Pro Tyr Leu Gly Leu Leu Leu Gln Gln Cys Trp
355 360 365
Ala Thr Pro Ser Thr Asp Pro Leu Ser Gln Pro Gln Trp Pro Ile Leu
370 375 380
Val Lys Gly Cys Pro Tyr Ile Gly Asp Asn Tyr Gln Thr Gln Leu Ile
385 390 395 400
Pro Val Gln Lys Ala Leu Asp Leu Pro Phe Pro Ser His His Gln Arg
405 410 415
Phe Ser Ile Phe Thr Phe Ser Phe Val Asn Pro Thr Val Glu Lys Gln
420 425 430
Ala Leu Arg Gly Pro Val His Leu His Cys Ser Val Ser Val Cys Gln
435 440 445
Pro Ala Glu Thr Pro Ser Cys Val Val Thr Cys Pro Asp Leu Ser Arg
450 455 460
Arg Arg Asn Phe Asp Asn Ser Ser Gln Asn Thr Thr Ala Ser Val Ser
465 470 475 480
Ser Lys Gly Pro Met Ile Leu Leu Gln Ala Thr Lys Asp Pro Pro Glu
485 490 495
Lys Leu Arg Val Pro Val Asp Ser Lys Val Leu Trp Val Ala Gly Leu
500 505 510
Ser Gly Thr Leu Ile Leu Gly Ala Leu Leu Val Ser Tyr Leu Ala Val
515 520 525
Lys Lys Gln Lys Ser Cys Pro Asp Gln Met Cys Gln
530 535 540
<210> 5
<211> 328
<212> PRT
<213> 智人
<400> 5
Gln Pro Leu Trp Leu Leu Gln Gly Gly Ala Ser His Pro Glu Thr Ser
1 5 10 15
Val Gln Pro Val Leu Val Glu Cys Gln Glu Ala Thr Leu Met Val Met
20 25 30
Val Ser Lys Asp Leu Phe Gly Thr Gly Lys Leu Ile Arg Ala Ala Asp
35 40 45
Leu Thr Leu Gly Pro Glu Ala Cys Glu Pro Leu Val Ser Met Asp Thr
50 55 60
Glu Asp Val Val Arg Phe Glu Val Gly Leu His Glu Cys Gly Asn Ser
65 70 75 80
Met Gln Val Thr Asp Asp Ala Leu Val Tyr Ser Thr Phe Leu Leu His
85 90 95
Asp Pro Arg Pro Val Gly Asn Leu Ser Ile Val Arg Thr Asn Arg Ala
100 105 110
Glu Ile Pro Ile Glu Cys Arg Tyr Pro Arg Gln Gly Asn Val Ser Ser
115 120 125
Gln Ala Ile Leu Pro Thr Trp Leu Pro Phe Arg Thr Thr Val Phe Ser
130 135 140
Glu Glu Lys Leu Thr Phe Ser Leu Arg Leu Met Glu Glu Asn Trp Asn
145 150 155 160
Ala Glu Lys Arg Ser Pro Thr Phe His Leu Gly Asp Ala Ala His Leu
165 170 175
Gln Ala Glu Ile His Thr Gly Ser His Val Pro Leu Arg Leu Phe Val
180 185 190
Asp His Cys Val Ala Thr Pro Thr Pro Asp Gln Asn Ala Ser Pro Tyr
195 200 205
His Thr Ile Val Asp Phe His Gly Cys Leu Val Asp Gly Leu Thr Asp
210 215 220
Ala Ser Ser Ala Phe Lys Val Pro Arg Pro Gly Pro Asp Thr Leu Gln
225 230 235 240
Phe Thr Val Asp Val Phe His Phe Ala Asn Asp Ser Arg Asn Met Ile
245 250 255
Tyr Ile Thr Cys His Leu Lys Val Thr Leu Ala Glu Gln Asp Pro Asp
260 265 270
Glu Leu Asn Lys Ala Cys Ser Phe Ser Lys Pro Ser Asn Ser Trp Phe
275 280 285
Pro Val Glu Gly Ser Ala Asp Ile Cys Gln Cys Cys Asn Lys Gly Asp
290 295 300
Cys Gly Thr Pro Ser His Ser Arg Arg Gln Pro His Val Met Ser Gln
305 310 315 320
Trp Ser Arg Ser Ala Ser Arg Asn
325
<210> 6
<211> 9
<212> PRT
<213> 智人
<400> 6
His Pro Glu Thr Ser Val Gln Pro Val
1 5
<210> 7
<211> 9
<212> PRT
<213> 智人
<400> 7
Pro Glu Thr Ser Val Gln Pro Val Leu
1 5
<210> 8
<211> 9
<212> PRT
<213> 智人
<400> 8
Gln Glu Ala Thr Leu Met Val Met Val
1 5
<210> 9
<211> 9
<212> PRT
<213> 智人
<400> 9
Ala Thr Leu Met Val Met Val Ser Lys
1 5
<210> 10
<211> 9
<212> PRT
<213> 智人
<400> 10
Leu Ile Arg Ala Ala Asp Leu Thr Leu
1 5
<210> 11
<211> 9
<212> PRT
<213> 智人
<400> 11
Thr Glu Asp Val Val Arg Phe Glu Val
1 5
<210> 12
<211> 9
<212> PRT
<213> 智人
<400> 12
Gln Val Thr Asp Asp Ala Leu Val Tyr
1 5
<210> 13
<211> 9
<212> PRT
<213> 智人
<400> 13
Ala Leu Val Tyr Ser Thr Phe Leu Leu
1 5
<210> 14
<211> 9
<212> PRT
<213> 智人
<400> 14
Phe Leu Leu His Asp Pro Arg Pro Val
1 5
<210> 15
<211> 9
<212> PRT
<213> 智人
<400> 15
Arg Pro Val Gly Asn Leu Ser Ile Val
1 5
<210> 16
<211> 9
<212> PRT
<213> 智人
<400> 16
Tyr Pro Arg Gln Gly Asn Val Ser Ser
1 5
<210> 17
<211> 9
<212> PRT
<213> 智人
<400> 17
Ser Ser Gln Ala Ile Leu Pro Thr Trp
1 5
<210> 18
<211> 9
<212> PRT
<213> 智人
<400> 18
Ala Ile Leu Pro Thr Trp Leu Pro Phe
1 5
<210> 19
<211> 9
<212> PRT
<213> 智人
<400> 19
Trp Leu Pro Phe Arg Thr Thr Val Phe
1 5
<210> 20
<211> 9
<212> PRT
<213> 智人
<400> 20
Val Phe Ser Glu Glu Lys Leu Thr Phe
1 5
<210> 21
<211> 9
<212> PRT
<213> 智人
<400> 21
Ser Glu Glu Lys Leu Thr Phe Ser Leu
1 5
<210> 22
<211> 9
<212> PRT
<213> 智人
<400> 22
Arg Leu Met Glu Glu Asn Trp Asn Ala
1 5
<210> 23
<211> 9
<212> PRT
<213> 智人
<400> 23
Phe His Leu Gly Asp Ala Ala His Leu
1 5
<210> 24
<211> 9
<212> PRT
<213> 智人
<400> 24
Ile His Thr Gly Ser His Val Pro Leu
1 5
<210> 25
<211> 9
<212> PRT
<213> 智人
<400> 25
Ser Pro Tyr His Thr Ile Val Asp Phe
1 5
<210> 26
<211> 9
<212> PRT
<213> 智人
<400> 26
Gly Leu Thr Asp Ala Ser Ser Ala Phe
1 5
<210> 27
<211> 9
<212> PRT
<213> 智人
<400> 27
Leu Thr Asp Ala Ser Ser Ala Phe Lys
1 5
<210> 28
<211> 9
<212> PRT
<213> 智人
<400> 28
Val Pro Arg Pro Gly Pro Asp Thr Leu
1 5
<210> 29
<211> 9
<212> PRT
<213> 智人
<400> 29
Arg Pro Gly Pro Asp Thr Leu Gln Phe
1 5
<210> 30
<211> 9
<212> PRT
<213> 智人
<400> 30
Gln Phe Thr Val Asp Val Phe His Phe
1 5
<210> 31
<211> 9
<212> PRT
<213> 智人
<400> 31
Phe Thr Val Asp Val Phe His Phe Ala
1 5
<210> 32
<211> 9
<212> PRT
<213> 智人
<400> 32
Ala Asn Asp Ser Arg Asn Met Ile Tyr
1 5
<210> 33
<211> 9
<212> PRT
<213> 智人
<400> 33
Met Ile Tyr Ile Thr Cys His Leu Lys
1 5
<210> 34
<211> 9
<212> PRT
<213> 智人
<400> 34
Ile Tyr Ile Thr Cys His Leu Lys Val
1 5
<210> 35
<211> 9
<212> PRT
<213> 智人
<400> 35
Phe Ser Lys Pro Ser Asn Ser Trp Phe
1 5
<210> 36
<211> 9
<212> PRT
<213> 智人
<400> 36
Lys Pro Ser Asn Ser Trp Phe Pro Val
1 5
<210> 37
<211> 9
<212> PRT
<213> 智人
<400> 37
Arg Gln Pro His Val Met Ser Gln Trp
1 5
<210> 38
<211> 9
<212> PRT
<213> 智人
<400> 38
Arg Gly Asp His Glu Val Glu Gln Trp
1 5
<210> 39
<211> 9
<212> PRT
<213> 智人
<400> 39
Glu Ala Thr Leu Met Val Met Val Ser
1 5
<210> 40
<211> 9
<212> PRT
<213> 智人
<400> 40
Leu Met Val Met Val Ser Lys Asp Leu
1 5
<210> 41
<211> 9
<212> PRT
<213> 智人
<400> 41
Met Val Met Val Ser Lys Asp Leu Phe
1 5
<210> 42
<211> 9
<212> PRT
<213> 智人
<400> 42
Leu Ile Arg Ala Ala Asp Leu Thr Leu
1 5
<210> 43
<211> 9
<212> PRT
<213> 智人
<400> 43
Leu Val Met Ser Asp Thr Glu Asp Val
1 5
<210> 44
<211> 9
<212> PRT
<213> 智人
<400> 44
Val Ser Met Asp Thr Glu Asp Val Val
1 5
<210> 45
<211> 9
<212> PRT
<213> 智人
<400> 45
Val Val Arg Phe Glu Val Gly Leu His
1 5
<210> 46
<211> 9
<212> PRT
<213> 智人
<400> 46
Gln Val Thr Asp Asp Ala Leu Val Tyr
1 5
<210> 47
<211> 9
<212> PRT
<213> 智人
<400> 47
Ala Leu Val Tyr Ser Thr Phe Leu Leu
1 5
<210> 48
<211> 9
<212> PRT
<213> 智人
<400> 48
Leu Val Tyr Ser Thr Phe Leu Leu His
1 5
<210> 49
<211> 9
<212> PRT
<213> 智人
<400> 49
Phe Leu Leu Asp Pro His Arg Pro Val
1 5
<210> 50
<211> 9
<212> PRT
<213> 智人
<400> 50
Leu Leu His Asp Pro Arg Pro Val Gly
1 5
<210> 51
<211> 9
<212> PRT
<213> 智人
<400> 51
Leu Ser Ile Val Arg Thr Asn Arg Ala
1 5
<210> 52
<211> 9
<212> PRT
<213> 智人
<400> 52
Ile Val Arg Thr Asn Arg Ala Glu Ile
1 5
<210> 53
<211> 9
<212> PRT
<213> 智人
<400> 53
Pro Phe Arg Thr Thr Val Phe Ser Glu
1 5
<210> 54
<211> 9
<212> PRT
<213> 智人
<400> 54
Phe Arg Thr Thr Val Phe Ser Glu Glu
1 5
<210> 55
<211> 9
<212> PRT
<213> 智人
<400> 55
Thr Phe Ser Leu Arg Leu Met Glu Glu
1 5
<210> 56
<211> 9
<212> PRT
<213> 智人
<400> 56
Phe His Leu Gly Asp Ala Ala His Leu
1 5
<210> 57
<211> 9
<212> PRT
<213> 智人
<400> 57
Leu Arg Leu Phe Val Asp His Cys Val
1 5
<210> 58
<211> 9
<212> PRT
<213> 智人
<400> 58
Leu Phe Val Asp His Cys Val Ala Thr
1 5
<210> 59
<211> 9
<212> PRT
<213> 智人
<400> 59
Gln Phe Thr Val Asp Val Phe His Phe
1 5
<210> 60
<211> 9
<212> PRT
<213> 智人
<400> 60
Phe Ala Asn Asp Ser Asn Arg Met Ile
1 5
<210> 61
<211> 9
<212> PRT
<213> 智人
<400> 61
Ile Tyr Ile Thr Cys His Leu Lys Val
1 5
<210> 62
<211> 9
<212> PRT
<213> 智人
<400> 62
Val Met Ser Gln Trp Ser Arg Ser Ala
1 5
<210> 63
<211> 9
<212> PRT
<213> 智人
<400> 63
Trp Ser Arg Ser Ala Ser Arg Asn Arg
1 5
<210> 64
<211> 9
<212> PRT
<213> 智人
<400> 64
Leu Ile Phe Leu Asp Arg Arg Gly Asp
1 5
<210> 65
<211> 9
<212> PRT
<213> 智人
<400> 65
Ile Phe Leu Asp Arg Arg Gly Asp His
1 5
<210> 66
<211> 49
<212> PRT
<213> 智人
<400> 66
Gly Gly Ala Ser His Pro Glu Thr Ser Val Gln Pro Val Leu Val Glu
1 5 10 15
Cys Gln Glu Ala Thr Leu Met Val Met Val Ser Lys Asp Leu Phe Gly
20 25 30
Thr Gly Lys Leu Ile Arg Ala Ala Asp Leu Thr Leu Gly Pro Glu Ala
35 40 45
Cys
<210> 67
<211> 26
<212> PRT
<213> 智人
<400> 67
Glu Ala Cys Glu Pro Leu Val Ser Met Asp Thr Glu Asp Val Val Arg
1 5 10 15
Phe Glu Val Gly Leu His Glu Cys Gly Asn
20 25
<210> 68
<211> 43
<212> PRT
<213> 智人
<400> 68
Cys Gly Asn Ser Met Gln Val Thr Asp Asp Ala Leu Val Tyr Ser Thr
1 5 10 15
Phe Leu Leu His Asp Pro Arg Pro Val Gly Asn Leu Ser Ile Val Arg
20 25 30
Thr Asn Arg Ala Glu Ile Pro Ile Glu Cys Arg
35 40
<210> 69
<211> 50
<212> PRT
<213> 智人
<400> 69
Ile Glu Cys Arg Tyr Pro Arg Gln Gly Asn Val Ser Ser Gln Ala Ile
1 5 10 15
Leu Pro Thr Trp Leu Pro Phe Arg Thr Thr Val Phe Ser Glu Glu Lys
20 25 30
Leu Thr Phe Ser Leu Arg Leu Met Glu Glu Asn Trp Asn Ala Glu Lys
35 40 45
Arg Ser
50
<210> 70
<211> 41
<212> PRT
<213> 智人
<400> 70
Lys Arg Ser Pro Thr Phe His Leu Gly Asp Ala Ala His Leu Gln Ala
1 5 10 15
Glu Ile His Thr Gly Ser His Val Pro Leu Arg Leu Phe Val Asp His
20 25 30
Cys Val Ala Thr Pro Thr Pro Asp Gln
35 40
<210> 71
<211> 44
<212> PRT
<213> 智人
<400> 71
Asp Gln Asn Ala Ser Pro Tyr His Thr Ile Val Asp Phe His Gly Cys
1 5 10 15
Leu Val Asp Gly Leu Thr Asp Ala Ser Ser Ala Phe Lys Val Pro Arg
20 25 30
Pro Gly Pro Asp Thr Leu Gln Phe Thr Val Asp Val
35 40
<210> 72
<211> 34
<212> PRT
<213> 智人
<400> 72
Gly Pro Asp Thr Leu Gln Phe Thr Val Asp Val Phe His Phe Ala Asn
1 5 10 15
Asp Ser Arg Asn Met Ile Tyr Ile Thr Cys His Leu Lys Val Thr Leu
20 25 30
Ala Glu
<210> 73
<211> 20
<212> PRT
<213> 智人
<400> 73
Lys Ala Cys Ser Phe Ser Lys Pro Ser Asn Ser Trp Phe Pro Val Glu
1 5 10 15
Gly Pro Ala Asp
20
<210> 74
<211> 27
<212> PRT
<213> 智人
<400> 74
Ser His Ser Arg Arg Gln Pro His Val Met Ser Gln Trp Ser Arg Ser
1 5 10 15
Ala Ser Arg Asn Arg Arg His Val Thr Glu Glu
20 25
<210> 75
<211> 26
<212> PRT
<213> 智人
<400> 75
Ala Asp Val Thr Val Gly Pro Leu Ile Phe Leu Asp Arg Arg Gly Asp
1 5 10 15
His Glu Val Glu Gln Trp Ala Leu Pro Ser
20 25
<210> 76
<211> 9
<212> PRT
<213> 智人
<400> 76
Phe Leu Leu His Asp Pro Arg Pro Val
1 5
<210> 77
<211> 9
<212> PRT
<213> 智人
<400> 77
Arg Leu Met Glu Glu Asn Trp Asn Ala
1 5
<210> 78
<211> 9
<212> PRT
<213> 智人
<400> 78
Ala Leu Val Tyr Ser Thr Phe Leu Leu
1 5
<210> 79
<211> 9
<212> PRT
<213> 智人
<400> 79
Phe Thr Val Asp Val Phe His Phe Ala
1 5
<210> 80
<211> 10
<212> PRT
<213> 智人
<400> 80
Leu Arg Leu Met Glu Glu Asn Trp Asn Ala
1 5 10
<210> 81
<211> 10
<212> PRT
<213> 智人
<400> 81
Phe Leu Asp Arg Arg Gly Asp His Glu Val
1 5 10
<210> 82
<211> 9
<212> PRT
<213> 智人
<400> 82
Cys Leu Val Asp Gly Leu Thr Asp Ala
1 5
<210> 83
<211> 9
<212> PRT
<213> 智人
<400> 83
Asn Met Ile Tyr Ile Thr Cys His Leu
1 5
<210> 84
<211> 10
<212> PRT
<213> 智人
<400> 84
Thr Phe Leu Leu His Asp Pro Arg Pro Val
1 5 10
<210> 85
<211> 10
<212> PRT
<213> 智人
<400> 85
Lys Leu Ile Arg Ala Ala Asp Leu Thr Leu
1 5 10
Claims (15)
1.一种药物组合物,其包含:
a)免疫原性多肽的来源,其包含来自人透明带蛋白(hZP)的氨基酸序列的I类MHC限制性表位和II类MHC限制性表位中的至少一种;
b)包含结合MHC-肽复合物的T细胞受体的T细胞,其中所述肽是来自hZP的氨基酸序列的肽;或者,
c)与hZP特异性结合的抗体或其片段;
其用于在人中的肺癌和/或其转移的治疗性和/或预防性治疗或诊断的方法中使用,其中优选地,所述hZP蛋白是人透明带3蛋白(hZP3)。
2.用于根据权利要求1使用的药物组合物,其中所述免疫原性多肽的来源是包含以下的组合物:
a)一种或多种免疫原性肽,其包含选自SEQ ID NO.66-75的氨基酸序列或由选自SEQID NO.66-75的氨基酸序列组成;和/或,
b)一种或多种免疫原性肽,包含选自SEQ ID NO.76-85的氨基酸序列或由选自SEQ IDNO.76-85的氨基酸序列组成。
3.用于根据权利要求1或2使用的药物组合物,其中所述治疗方法是预防肺癌的转移和/或复发的方法,其中优选地,所述肺癌是非小细胞肺癌。
4.用于根据权利要求1-3中任一项使用的药物组合物,其中所述治疗方法与免疫调节疗法、手术、放射疗法、化学疗法、靶向疗法或其组合相组合。
5.用于根据权利要求4使用的药物组合物,其中所述免疫调节疗法包含使用以下中的至少一种:检查点抑制剂、靶向TNF受体家族成员的抗体、免疫抑制性细胞因子、γC细胞因子、TLR激动剂和iNKT细胞的激动剂。
6.用于根据前述权利要求中任一项使用的药物组合物,其中所述免疫原性多肽的来源包括以下中的至少一种:
a)蛋白质组合物,其包含如权利要求1中定义的至少一种免疫原性多肽;
b)编码所述免疫原性多肽的氨基酸序列的核酸分子;
c)表达所述免疫原性多肽的细胞;和,
d)呈递MHC-肽复合物的抗原呈递细胞,其中所述肽是来自hZP的氨基酸序列的肽。
7.用于根据权利要求6使用的药物组合物,其中:
a)所述蛋白质组合物包含至少一种免疫原性多肽,其包含选自hZP的氨基酸序列的至少18个氨基酸的邻接氨基酸序列,并且其中所述邻接氨基酸序列包含I类MHC和II类MHC限制性T细胞表位中的至少一种;
b)所述核酸分子是:
i)DNA分子,其是用于在人细胞中表达所述免疫原性多肽的表达构建体;或者,
ii)能够在人细胞中被翻译成所述免疫原性多肽的RNA分子;
c)所述细胞是微生物细胞,优选李斯特菌属(Listeria)细胞;和,
d)所述抗原呈递细胞是自体或同种异体树突状细胞,其离体负载有如权利要求1中定义的免疫原性多肽。
8.用于根据权利要求7使用的药物组合物,其中所述蛋白质组合物包含多于一种不同的免疫原性多肽,各自包含选自hZP的氨基酸序列中的至少18个氨基酸的邻接氨基酸序列,并且具有在18-100个氨基酸的范围内的长度,优选在18-60个氨基酸的范围内的长度。
9.用于根据前述权利要求中任一项使用的药物组合物,其中所述hZP是hZP3(23-350)。
10.用于根据前述权利要求中任一项使用的药物组合物,其中所述一种或多种免疫原性肽的来源共同包含以下中的至少一种:
a)hZP3或hZP3(23-350)的完整氨基酸序列的至少50、70、80、90或95%;和,
b)通过基于计算机的算法生物信息学工具预测至少50、70、80、90或95%的潜在MHC I和/或MHC II表位。
11.一种用于根据前述权利要求中任一项使用的药物组合物,其中所述方法进一步包括至少一种佐剂的施用,优选共施用。
12.一种用于根据前述权利要求中任一项使用的药物组合物,其中所述治疗方法包括施用有效量的所述组合物,其中所述组合物通过以下中的至少一种施用:肿瘤内、肌内、腹膜内、真皮内、皮下、经皮施用、以及施用到引流到至少一个***盆内的解剖部位内。
13.一种用于根据权利要求1-5中任一项使用的药物组合物,其中所述抗体或其片段是与hZP3(23-350)特异性结合的人源化或人单克隆抗体或其片段。
14.一种用于根据权利要求13使用的药物组合物,其中所述抗体或其片段与以下中的至少一种缀合:细胞毒性剂、细胞生长抑制剂、放射性核素、含有放射性核素的部分、可检测试剂和显像剂,优选体内显像剂。
15.一种用于根据权利要求14使用的药物组合物,其中所述放射性核素选自125I、123I、111In、177Lu、90Y、213Bi、225Ac和99mTc。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP17199441 | 2017-10-31 | ||
EP17199441.1 | 2017-10-31 | ||
PCT/EP2018/079802 WO2019086507A1 (en) | 2017-10-31 | 2018-10-31 | Immunotherapeutic methods for treating and/or preventing lung cancer |
Publications (1)
Publication Number | Publication Date |
---|---|
CN111511392A true CN111511392A (zh) | 2020-08-07 |
Family
ID=60421550
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201880083511.0A Pending CN111511392A (zh) | 2017-10-31 | 2018-10-31 | 用于治疗和/或预防肺癌的免疫治疗方法 |
Country Status (6)
Country | Link |
---|---|
US (1) | US11819542B2 (zh) |
EP (1) | EP3703734A1 (zh) |
CN (1) | CN111511392A (zh) |
BR (1) | BR112020008512A2 (zh) |
CA (1) | CA3080835A1 (zh) |
WO (1) | WO2019086507A1 (zh) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20210317165A1 (en) * | 2018-09-03 | 2021-10-14 | Laboratoire Hra-Pharma | Zp3 fragments in immunotherapy of ovarian cancer |
WO2023066923A1 (en) | 2021-10-19 | 2023-04-27 | Rahman Nafis | Male contraception |
WO2023237726A1 (en) * | 2022-06-10 | 2023-12-14 | Pantarhei Oncology B.V. | An intracellular tumor-specific variant of human zona pellucida glycoprotein 3 and nucleic acids coding therefor for use in the treatment of cancer |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012026820A2 (en) * | 2010-08-27 | 2012-03-01 | Pantarhei Bioscience B.V. | Immunotherapeutic method for treating prostate cancer |
WO2017097699A1 (en) * | 2015-12-11 | 2017-06-15 | Immatics Biotechnologies Gmbh | Novel peptides and combination of peptides for use in immunotherapy against various cancers |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2777890B1 (fr) | 1998-04-22 | 2000-12-29 | Roussy Inst Gustave | Composes peptidiques d'hsp70 utiles dans l'immunotherapie du cancer |
AU2002219711B8 (en) | 2000-12-08 | 2006-03-02 | Academisch Ziekenhuis Leiden | Long peptides of 22-45 amino acid residues that induce and/or enhance antigen specific immune responses |
TWI329130B (en) | 2003-06-19 | 2010-08-21 | Bestewil Holding Bv | Functionally reconstituted viral membranes containing adjuvant |
CA2724018C (en) | 2008-05-19 | 2017-01-10 | Dcprime B.V. | Method for inducing and accelerating cells |
WO2013087083A1 (en) | 2011-12-15 | 2013-06-20 | Biontech Ag | Particles comprising single stranded rna and double stranded rna for immunomodulation |
NL2009102C2 (en) | 2012-07-02 | 2014-01-06 | Dcprime B V | Method for dc-loading. |
EP2743344A1 (en) | 2012-12-11 | 2014-06-18 | DCPrime B.V. | Therapeutic cancer vaccines derived from a novel dendritic cell line |
WO2014165291A1 (en) | 2013-03-12 | 2014-10-09 | The Trustees Of The University Of Pennsylvania | Improved vaccines for human papilloma virus and methods for using the same |
WO2015164121A1 (en) | 2014-04-24 | 2015-10-29 | Advaxis, Inc. | Recombinant listeria vaccine strains and methods of producing the same |
KR102485788B1 (ko) | 2014-08-27 | 2023-01-09 | 메모리얼 슬로안 케터링 캔서 센터 | 항체, 조성물 및 용도 |
CA2974956A1 (en) | 2015-01-29 | 2016-08-04 | The Trustees Of The University Of Pennsylvania | Checkpoint inhibitor and vaccine combinations and use of same for immunotherapy |
AU2017214656B2 (en) | 2016-02-05 | 2022-08-25 | Inovio Pharmaceuticals, Inc. | Cancer vaccines and methods of treatment using the same |
US20190307868A1 (en) | 2016-03-31 | 2019-10-10 | Neon Therapeutics, Inc. | Neoantigens and methods of their use |
-
2018
- 2018-10-31 CA CA3080835A patent/CA3080835A1/en active Pending
- 2018-10-31 BR BR112020008512-0A patent/BR112020008512A2/pt unknown
- 2018-10-31 WO PCT/EP2018/079802 patent/WO2019086507A1/en unknown
- 2018-10-31 CN CN201880083511.0A patent/CN111511392A/zh active Pending
- 2018-10-31 US US16/760,457 patent/US11819542B2/en active Active
- 2018-10-31 EP EP18795630.5A patent/EP3703734A1/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012026820A2 (en) * | 2010-08-27 | 2012-03-01 | Pantarhei Bioscience B.V. | Immunotherapeutic method for treating prostate cancer |
WO2017097699A1 (en) * | 2015-12-11 | 2017-06-15 | Immatics Biotechnologies Gmbh | Novel peptides and combination of peptides for use in immunotherapy against various cancers |
Non-Patent Citations (1)
Title |
---|
NAFIS A. RAHMAN等: "A novel treatment strategy for ovarian cancer based on immunization against zona pellucida protein (ZP) 3", 《THE FASEB JOURNAL》, vol. 26, pages 324 - 333, XP002756672, DOI: 10.1096/fj.11-192468 * |
Also Published As
Publication number | Publication date |
---|---|
EP3703734A1 (en) | 2020-09-09 |
CA3080835A1 (en) | 2019-05-09 |
US20200276291A1 (en) | 2020-09-03 |
RU2020117746A (ru) | 2021-12-01 |
BR112020008512A2 (pt) | 2020-10-06 |
WO2019086507A1 (en) | 2019-05-09 |
US11819542B2 (en) | 2023-11-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20210154279A1 (en) | Target peptides for colorectal cancer therapy and diagnostics | |
JP2019194180A (ja) | Micaおよびmicbタンパク質に対する抗体 | |
JP5291641B2 (ja) | 癌抗原及びその利用 | |
AU2020204594A1 (en) | Target peptides for ovarian cancer therapy and diagnostics | |
UA121112C2 (uk) | Антитіло до ox40 та його застосування | |
JP6796123B2 (ja) | Xbp1ペプチド、cd138ペプチドおよびcs1ペプチド | |
AU2019252795A1 (en) | Anticancer combination therapy with cd73 antagonist antibody and pd-1/pd-l1 axis antagonist antibody | |
CA2883569A1 (en) | Target peptides for immunotherapy and diagnostics | |
TW201705968A (zh) | 用於治療胰臟癌之pd-1拮抗劑與基於李斯特菌屬之疫苗的組合 | |
JP2019532023A (ja) | ヒト抗体、医薬組成物及び方法 | |
JP2003524021A (ja) | 悪性中皮腫の診断および治療のための組成物および方法 | |
JP2018512397A (ja) | 癌治療の有効性を高めるための組成物及び方法 | |
US11819542B2 (en) | Immunotherapeutic method for treating lung cancer by administering a polypeptide comprising an epitope of hZP3 | |
US20190015494A1 (en) | Identification of class i mhc associated glycopeptides as targets for cancer immunotherapy | |
TW202142257A (zh) | 用pd-1軸結合拮抗劑及rna疫苗誘導新抗原決定基特異性t細胞之方法 | |
US20230279073A1 (en) | Peptides and combinations of peptides for use in immunotherapy against hematologic neoplasms and other cancers | |
TW201416374A (zh) | 對於th1細胞之ly6k抗原決定位胜肽及含此之疫苗 | |
RU2793972C2 (ru) | Иммунотерапевтический способ лечения и/или профилактики рака легких | |
BRPI0717142A2 (pt) | Composição terapêutica e kit de reativos para uso terapêutico | |
WO2021016249A2 (en) | Target peptides for cancer therapy and diagnostics | |
Garrett | Peptide-based B-cell epitope vaccines targeting HER-2/neu | |
CN115956088A (zh) | 包括抗-CD19抗体和阻断SIRPα-CD47先天免疫检查点的多肽的抗肿瘤组合疗法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |