CN112851770A - 一种用于诊断或防治金黄色葡萄球菌感染的α溶血素抗原表位肽及其应用 - Google Patents
一种用于诊断或防治金黄色葡萄球菌感染的α溶血素抗原表位肽及其应用 Download PDFInfo
- Publication number
- CN112851770A CN112851770A CN202110163653.1A CN202110163653A CN112851770A CN 112851770 A CN112851770 A CN 112851770A CN 202110163653 A CN202110163653 A CN 202110163653A CN 112851770 A CN112851770 A CN 112851770A
- Authority
- CN
- China
- Prior art keywords
- staphylococcus aureus
- epitope peptide
- antibody
- hemolysin
- thr
- 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.)
- Granted
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 92
- 206010041925 Staphylococcal infections Diseases 0.000 title claims abstract description 27
- 208000015339 staphylococcus aureus infection Diseases 0.000 title claims abstract description 22
- 101710092462 Alpha-hemolysin Proteins 0.000 title claims description 18
- 241000191967 Staphylococcus aureus Species 0.000 claims abstract description 124
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 24
- 239000003814 drug Substances 0.000 claims abstract description 13
- 229920001184 polypeptide Polymers 0.000 claims abstract description 10
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 9
- 238000002360 preparation method Methods 0.000 claims abstract description 3
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 4
- 238000001514 detection method Methods 0.000 claims description 12
- 108010045069 keyhole-limpet hemocyanin Proteins 0.000 claims description 11
- 239000002671 adjuvant Substances 0.000 claims description 7
- 108020001507 fusion proteins Proteins 0.000 claims description 7
- 102000037865 fusion proteins Human genes 0.000 claims description 7
- 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 claims description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 claims description 4
- 241000283707 Capra Species 0.000 claims description 4
- 102000014914 Carrier Proteins Human genes 0.000 claims description 4
- 108010078791 Carrier Proteins Proteins 0.000 claims description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 claims description 4
- 229940098773 bovine serum albumin Drugs 0.000 claims description 4
- 230000000890 antigenic effect Effects 0.000 claims description 3
- 102000008946 Fibrinogen Human genes 0.000 claims description 2
- 108010049003 Fibrinogen Proteins 0.000 claims description 2
- 108010010803 Gelatin Proteins 0.000 claims description 2
- 239000004793 Polystyrene Substances 0.000 claims description 2
- 102000009843 Thyroglobulin Human genes 0.000 claims description 2
- 108010034949 Thyroglobulin Proteins 0.000 claims description 2
- 239000011324 bead Substances 0.000 claims description 2
- 229960002685 biotin Drugs 0.000 claims description 2
- 235000020958 biotin Nutrition 0.000 claims description 2
- 239000011616 biotin Substances 0.000 claims description 2
- 238000003745 diagnosis Methods 0.000 claims description 2
- 229940012952 fibrinogen Drugs 0.000 claims description 2
- 239000007850 fluorescent dye Substances 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 239000008273 gelatin Substances 0.000 claims description 2
- 229940014259 gelatin Drugs 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- 235000011852 gelatine desserts Nutrition 0.000 claims description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims description 2
- 229920002223 polystyrene Polymers 0.000 claims description 2
- 229960002175 thyroglobulin Drugs 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 230000002265 prevention Effects 0.000 claims 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 208000015181 infectious disease Diseases 0.000 abstract description 11
- 102000036639 antigens Human genes 0.000 abstract description 7
- 108091007433 antigens Proteins 0.000 abstract description 7
- 239000000427 antigen Substances 0.000 abstract description 6
- 239000003228 hemolysin Substances 0.000 abstract description 6
- 108010006464 Hemolysin Proteins Proteins 0.000 abstract description 5
- 238000012216 screening Methods 0.000 abstract description 5
- 230000005847 immunogenicity Effects 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 2
- 150000001413 amino acids Chemical class 0.000 description 15
- 241000699666 Mus <mouse, genus> Species 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 9
- 230000003053 immunization Effects 0.000 description 9
- 238000005406 washing Methods 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 7
- 210000003719 b-lymphocyte Anatomy 0.000 description 7
- 238000002649 immunization Methods 0.000 description 7
- 229960005486 vaccine Drugs 0.000 description 7
- 108010040443 aspartyl-aspartic acid Proteins 0.000 description 6
- 108010069205 aspartyl-phenylalanine Proteins 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- JNGHLWWFPGIJER-STQMWFEESA-N Gly-Pro-Tyr Chemical compound NCC(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 JNGHLWWFPGIJER-STQMWFEESA-N 0.000 description 4
- RPWQJSBMXJSCPD-XUXIUFHCSA-N Lys-Val-Ile Chemical compound CC[C@H](C)[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CCCCN)C(C)C)C(O)=O RPWQJSBMXJSCPD-XUXIUFHCSA-N 0.000 description 4
- VWFHWJGVLVZVIS-QXEWZRGKSA-N Met-Val-Asn Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O VWFHWJGVLVZVIS-QXEWZRGKSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 208000037942 Methicillin-resistant Staphylococcus aureus infection Diseases 0.000 description 4
- 108010079364 N-glycylalanine Proteins 0.000 description 4
- 230000003115 biocidal effect Effects 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 108010064235 lysylglycine Proteins 0.000 description 4
- 230000001717 pathogenic effect Effects 0.000 description 4
- 108010061238 threonyl-glycine Proteins 0.000 description 4
- ZIBWKCRKNFYTPT-ZKWXMUAHSA-N Ala-Asn-Val Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O ZIBWKCRKNFYTPT-ZKWXMUAHSA-N 0.000 description 3
- FVSOUJZKYWEFOB-KBIXCLLPSA-N Ala-Gln-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)N FVSOUJZKYWEFOB-KBIXCLLPSA-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
- ATHZHGQSAIJHQU-XIRDDKMYSA-N Asn-Trp-Lys Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)N)N ATHZHGQSAIJHQU-XIRDDKMYSA-N 0.000 description 3
- FAEIQWHBRBWUBN-FXQIFTODSA-N Asp-Arg-Ser Chemical compound C(C[C@@H](C(=O)N[C@@H](CO)C(=O)O)NC(=O)[C@H](CC(=O)O)N)CN=C(N)N FAEIQWHBRBWUBN-FXQIFTODSA-N 0.000 description 3
- QNMKWNONJGKJJC-NHCYSSNCSA-N Asp-Leu-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(O)=O QNMKWNONJGKJJC-NHCYSSNCSA-N 0.000 description 3
- NVFSJIXJZCDICF-SRVKXCTJSA-N Asp-Lys-Lys Chemical compound C(CCN)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)O)N NVFSJIXJZCDICF-SRVKXCTJSA-N 0.000 description 3
- NAAAPCLFJPURAM-HJGDQZAQSA-N Asp-Thr-Lys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)O)N)O NAAAPCLFJPURAM-HJGDQZAQSA-N 0.000 description 3
- UXRVDHVARNBOIO-QSFUFRPTSA-N Asp-Val-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(=O)O)N UXRVDHVARNBOIO-QSFUFRPTSA-N 0.000 description 3
- 238000011725 BALB/c mouse Methods 0.000 description 3
- DXMPMSWUZVNBSG-QEJZJMRPSA-N Gln-Asn-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCC(=O)N)N DXMPMSWUZVNBSG-QEJZJMRPSA-N 0.000 description 3
- DOQUICBEISTQHE-CIUDSAMLSA-N Gln-Pro-Asp Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O DOQUICBEISTQHE-CIUDSAMLSA-N 0.000 description 3
- WJZLEENECIOOSA-WDSKDSINSA-N Gly-Asn-Gln Chemical compound NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)O WJZLEENECIOOSA-WDSKDSINSA-N 0.000 description 3
- FUTAPPOITCCWTH-WHFBIAKZSA-N Gly-Asp-Asp Chemical compound [H]NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O FUTAPPOITCCWTH-WHFBIAKZSA-N 0.000 description 3
- LYSVCKOXIDKEEL-SRVKXCTJSA-N His-Asn-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CC1=CN=CN1 LYSVCKOXIDKEEL-SRVKXCTJSA-N 0.000 description 3
- CCUSLCQWVMWTIS-IXOXFDKPSA-N His-Thr-Leu Chemical compound [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O CCUSLCQWVMWTIS-IXOXFDKPSA-N 0.000 description 3
- CDGLBYSAZFIIJO-RCOVLWMOSA-N Ile-Gly-Gly Chemical compound CC[C@H](C)[C@H]([NH3+])C(=O)NCC(=O)NCC([O-])=O CDGLBYSAZFIIJO-RCOVLWMOSA-N 0.000 description 3
- HUORUFRRJHELPD-MNXVOIDGSA-N Ile-Leu-Glu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)O)N HUORUFRRJHELPD-MNXVOIDGSA-N 0.000 description 3
- LKXANTUNFMVCNF-IHPCNDPISA-N Leu-His-Trp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O LKXANTUNFMVCNF-IHPCNDPISA-N 0.000 description 3
- BMVFXOQHDQZAQU-DCAQKATOSA-N Leu-Pro-Asp Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)O)N BMVFXOQHDQZAQU-DCAQKATOSA-N 0.000 description 3
- MRWXLRGAFDOILG-DCAQKATOSA-N Lys-Gln-Gln Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O MRWXLRGAFDOILG-DCAQKATOSA-N 0.000 description 3
- ZXEUFAVXODIPHC-GUBZILKMSA-N Lys-Glu-Asn Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O ZXEUFAVXODIPHC-GUBZILKMSA-N 0.000 description 3
- QQPSCXKFDSORFT-IHRRRGAJSA-N Lys-Lys-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCCN QQPSCXKFDSORFT-IHRRRGAJSA-N 0.000 description 3
- TVHCDSBMFQYPNA-RHYQMDGZSA-N Lys-Thr-Arg Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O TVHCDSBMFQYPNA-RHYQMDGZSA-N 0.000 description 3
- SQUTUWHAAWJYES-GUBZILKMSA-N Met-Asp-Arg Chemical compound [H]N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O SQUTUWHAAWJYES-GUBZILKMSA-N 0.000 description 3
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 3
- BKWJQWJPZMUWEG-LFSVMHDDSA-N Phe-Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=CC=C1 BKWJQWJPZMUWEG-LFSVMHDDSA-N 0.000 description 3
- HTTYNOXBBOWZTB-SRVKXCTJSA-N Phe-Asn-Asn Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(=O)N)C(=O)O)N HTTYNOXBBOWZTB-SRVKXCTJSA-N 0.000 description 3
- HHOOEUSPFGPZFP-QWRGUYRKSA-N Phe-Asn-Gly Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(O)=O HHOOEUSPFGPZFP-QWRGUYRKSA-N 0.000 description 3
- GYEPCBNTTRORKW-PCBIJLKTSA-N Phe-Ile-Asp Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(O)=O GYEPCBNTTRORKW-PCBIJLKTSA-N 0.000 description 3
- GPSMLZQVIIYLDK-ULQDDVLXSA-N Phe-Lys-Val Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(O)=O GPSMLZQVIIYLDK-ULQDDVLXSA-N 0.000 description 3
- JFWDJFULOLKQFY-QWRGUYRKSA-N Ser-Gly-Phe Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O JFWDJFULOLKQFY-QWRGUYRKSA-N 0.000 description 3
- NADLKBTYNKUJEP-KATARQTJSA-N Ser-Thr-Leu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(O)=O NADLKBTYNKUJEP-KATARQTJSA-N 0.000 description 3
- AXKJPUBALUNJEO-UBHSHLNASA-N Ser-Trp-Asn Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(N)=O)C(O)=O AXKJPUBALUNJEO-UBHSHLNASA-N 0.000 description 3
- XOWKUMFHEZLKLT-CIQUZCHMSA-N Thr-Ile-Ala Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O XOWKUMFHEZLKLT-CIQUZCHMSA-N 0.000 description 3
- ZSPQUTWLWGWTPS-HJGDQZAQSA-N Thr-Lys-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(O)=O ZSPQUTWLWGWTPS-HJGDQZAQSA-N 0.000 description 3
- LECUEEHKUFYOOV-ZJDVBMNYSA-N Thr-Thr-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](N)[C@@H](C)O LECUEEHKUFYOOV-ZJDVBMNYSA-N 0.000 description 3
- 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 3
- NMANTMWGQZASQN-QXEWZRGKSA-N Val-Arg-Asp Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(=O)O)C(=O)O)N NMANTMWGQZASQN-QXEWZRGKSA-N 0.000 description 3
- KDKLLPMFFGYQJD-CYDGBPFRSA-N Val-Ile-Arg Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](C(C)C)N KDKLLPMFFGYQJD-CYDGBPFRSA-N 0.000 description 3
- 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 3
- 108010047495 alanylglycine Proteins 0.000 description 3
- 108010062796 arginyllysine Proteins 0.000 description 3
- 108010077245 asparaginyl-proline Proteins 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 108010026364 glycyl-glycyl-leucine Proteins 0.000 description 3
- 230000002949 hemolytic effect Effects 0.000 description 3
- 108010044374 isoleucyl-tyrosine Proteins 0.000 description 3
- 108010034529 leucyl-lysine Proteins 0.000 description 3
- 108010025153 lysyl-alanyl-alanine Proteins 0.000 description 3
- 108010054155 lysyllysine Proteins 0.000 description 3
- 108010017391 lysylvaline Proteins 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 229960003085 meticillin Drugs 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 108010031491 threonyl-lysyl-glutamic acid Proteins 0.000 description 3
- 108010038745 tryptophylglycine Proteins 0.000 description 3
- 108010071635 tyrosyl-prolyl-arginine Proteins 0.000 description 3
- 108010073969 valyllysine Proteins 0.000 description 3
- OTLLEIBWKHEHGU-UHFFFAOYSA-N 2-[5-[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy]-3,4-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-4-phosphonooxyhexanedioic acid Chemical compound C1=NC=2C(N)=NC=NC=2N1C(C(C1O)O)OC1COC1C(CO)OC(OC(C(O)C(OP(O)(O)=O)C(O)C(O)=O)C(O)=O)C(O)C1O OTLLEIBWKHEHGU-UHFFFAOYSA-N 0.000 description 2
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 2
- XQGIRPGAVLFKBJ-CIUDSAMLSA-N Ala-Asn-Lys Chemical compound N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)O XQGIRPGAVLFKBJ-CIUDSAMLSA-N 0.000 description 2
- DMLSCRJBWUEALP-LAEOZQHASA-N Asn-Glu-Val Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O DMLSCRJBWUEALP-LAEOZQHASA-N 0.000 description 2
- NPZJLGMWMDNQDD-GHCJXIJMSA-N Asn-Ser-Ile Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O NPZJLGMWMDNQDD-GHCJXIJMSA-N 0.000 description 2
- 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 2
- ZLGKHJHFYSRUBH-FXQIFTODSA-N Asp-Arg-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O ZLGKHJHFYSRUBH-FXQIFTODSA-N 0.000 description 2
- 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 2
- OYSYWMMZGJSQRB-AVGNSLFASA-N Asp-Tyr-Gln Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(O)=O OYSYWMMZGJSQRB-AVGNSLFASA-N 0.000 description 2
- 208000031729 Bacteremia Diseases 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- LGIKBBLQVSWUGK-DCAQKATOSA-N Gln-Leu-Gln Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O LGIKBBLQVSWUGK-DCAQKATOSA-N 0.000 description 2
- MPZWMIIOPAPAKE-BQBZGAKWSA-N Glu-Arg Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=N MPZWMIIOPAPAKE-BQBZGAKWSA-N 0.000 description 2
- SJPMNHCEWPTRBR-BQBZGAKWSA-N Glu-Glu-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(O)=O SJPMNHCEWPTRBR-BQBZGAKWSA-N 0.000 description 2
- QEJKKJNDDDPSMU-KKUMJFAQSA-N Glu-Tyr-Met Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCSC)C(O)=O QEJKKJNDDDPSMU-KKUMJFAQSA-N 0.000 description 2
- JLJLBWDKDRYOPA-RYUDHWBXSA-N Gly-Gln-Tyr Chemical compound NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 JLJLBWDKDRYOPA-RYUDHWBXSA-N 0.000 description 2
- YHYDTTUSJXGTQK-UWVGGRQHSA-N Gly-Met-Leu Chemical compound CSCC[C@H](NC(=O)CN)C(=O)N[C@@H](CC(C)C)C(O)=O YHYDTTUSJXGTQK-UWVGGRQHSA-N 0.000 description 2
- IALQAMYQJBZNSK-WHFBIAKZSA-N Gly-Ser-Asn Chemical compound [H]NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O IALQAMYQJBZNSK-WHFBIAKZSA-N 0.000 description 2
- YABRDIBSPZONIY-BQBZGAKWSA-N Gly-Ser-Met Chemical compound [H]NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(O)=O YABRDIBSPZONIY-BQBZGAKWSA-N 0.000 description 2
- FKESCSGWBPUTPN-FOHZUACHSA-N Gly-Thr-Asn Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(O)=O FKESCSGWBPUTPN-FOHZUACHSA-N 0.000 description 2
- JBCLFWXMTIKCCB-UHFFFAOYSA-N H-Gly-Phe-OH Natural products NCC(=O)NC(C(O)=O)CC1=CC=CC=C1 JBCLFWXMTIKCCB-UHFFFAOYSA-N 0.000 description 2
- UCGDDTHMMVWVMV-FSPLSTOPSA-N Ile-Gly Chemical compound CC[C@H](C)[C@H](N)C(=O)NCC(O)=O UCGDDTHMMVWVMV-FSPLSTOPSA-N 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- HXWALXSAVBLTPK-NUTKFTJISA-N Leu-Ala-Trp Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CC(C)C)N HXWALXSAVBLTPK-NUTKFTJISA-N 0.000 description 2
- QJXHMYMRGDOHRU-NHCYSSNCSA-N Leu-Ile-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(O)=O QJXHMYMRGDOHRU-NHCYSSNCSA-N 0.000 description 2
- RXGLHDWAZQECBI-SRVKXCTJSA-N Leu-Leu-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O RXGLHDWAZQECBI-SRVKXCTJSA-N 0.000 description 2
- WXDRGWBQZIMJDE-ULQDDVLXSA-N Leu-Phe-Met Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCSC)C(O)=O WXDRGWBQZIMJDE-ULQDDVLXSA-N 0.000 description 2
- FZIJIFCXUCZHOL-CIUDSAMLSA-N Lys-Ala-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCCCN FZIJIFCXUCZHOL-CIUDSAMLSA-N 0.000 description 2
- KNKHAVVBVXKOGX-JXUBOQSCSA-N Lys-Ala-Thr Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O KNKHAVVBVXKOGX-JXUBOQSCSA-N 0.000 description 2
- ZXFRGTAIIZHNHG-AJNGGQMLSA-N Lys-Ile-Leu Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)O)NC(=O)[C@H](CCCCN)N ZXFRGTAIIZHNHG-AJNGGQMLSA-N 0.000 description 2
- JHNOXVASMSXSNB-WEDXCCLWSA-N Lys-Thr-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O JHNOXVASMSXSNB-WEDXCCLWSA-N 0.000 description 2
- BIWVMACFGZFIEB-VFAJRCTISA-N Lys-Trp-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CC1=CNC2=CC=CC=C21)NC(=O)[C@H](CCCCN)N)O BIWVMACFGZFIEB-VFAJRCTISA-N 0.000 description 2
- VVURYEVJJTXWNE-ULQDDVLXSA-N Lys-Tyr-Val Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C(C)C)C(O)=O VVURYEVJJTXWNE-ULQDDVLXSA-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
- XZQYIJALMGEUJD-OEAJRASXSA-N Phe-Lys-Thr Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XZQYIJALMGEUJD-OEAJRASXSA-N 0.000 description 2
- APMXLWHMIVWLLR-BZSNNMDCSA-N Phe-Tyr-Ser Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(O)=O)C1=CC=CC=C1 APMXLWHMIVWLLR-BZSNNMDCSA-N 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- 108010039918 Polylysine Proteins 0.000 description 2
- MTHRMUXESFIAMS-DCAQKATOSA-N Pro-Asn-Lys Chemical compound C1C[C@H](NC1)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)O MTHRMUXESFIAMS-DCAQKATOSA-N 0.000 description 2
- POQFNPILEQEODH-FXQIFTODSA-N Pro-Ser-Ala Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O POQFNPILEQEODH-FXQIFTODSA-N 0.000 description 2
- PGSWNLRYYONGPE-JYJNAYRXSA-N Pro-Val-Tyr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O PGSWNLRYYONGPE-JYJNAYRXSA-N 0.000 description 2
- 206010040070 Septic Shock Diseases 0.000 description 2
- HEQPKICPPDOSIN-SRVKXCTJSA-N Ser-Asp-Tyr Chemical compound OC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 HEQPKICPPDOSIN-SRVKXCTJSA-N 0.000 description 2
- PVDTYLHUWAEYGY-CIUDSAMLSA-N Ser-Glu-Arg Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O PVDTYLHUWAEYGY-CIUDSAMLSA-N 0.000 description 2
- WSTIOCFMWXNOCX-YUMQZZPRSA-N Ser-Gly-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CO)N WSTIOCFMWXNOCX-YUMQZZPRSA-N 0.000 description 2
- IFPBAGJBHSNYPR-ZKWXMUAHSA-N Ser-Ile-Gly Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(O)=O IFPBAGJBHSNYPR-ZKWXMUAHSA-N 0.000 description 2
- PJIQEIFXZPCWOJ-FXQIFTODSA-N Ser-Pro-Asp Chemical compound [H]N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(O)=O)C(O)=O PJIQEIFXZPCWOJ-FXQIFTODSA-N 0.000 description 2
- FLONGDPORFIVQW-XGEHTFHBSA-N Ser-Pro-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CO FLONGDPORFIVQW-XGEHTFHBSA-N 0.000 description 2
- UQTNIFUCMBFWEJ-IWGUZYHVSA-N Thr-Asn Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(O)=O)CC(N)=O UQTNIFUCMBFWEJ-IWGUZYHVSA-N 0.000 description 2
- CTONFVDJYCAMQM-IUKAMOBKSA-N Thr-Asn-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H]([C@@H](C)O)N CTONFVDJYCAMQM-IUKAMOBKSA-N 0.000 description 2
- GKMYGVQDGVYCPC-IUKAMOBKSA-N Thr-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H]([C@@H](C)O)N GKMYGVQDGVYCPC-IUKAMOBKSA-N 0.000 description 2
- JLNMFGCJODTXDH-WEDXCCLWSA-N Thr-Lys-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)NCC(O)=O JLNMFGCJODTXDH-WEDXCCLWSA-N 0.000 description 2
- 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 2
- BZTSQFWJNJYZSX-JRQIVUDYSA-N Thr-Tyr-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O BZTSQFWJNJYZSX-JRQIVUDYSA-N 0.000 description 2
- PELIQFPESHBTMA-WLTAIBSBSA-N Thr-Tyr-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@H](C(=O)NCC(O)=O)CC1=CC=C(O)C=C1 PELIQFPESHBTMA-WLTAIBSBSA-N 0.000 description 2
- 206010044248 Toxic shock syndrome Diseases 0.000 description 2
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 2
- XQYHLZNPOTXRMQ-KKUMJFAQSA-N Tyr-Glu-Arg Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O XQYHLZNPOTXRMQ-KKUMJFAQSA-N 0.000 description 2
- GYKDRHDMGQUZPU-MGHWNKPDSA-N Tyr-Lys-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC1=CC=C(C=C1)O)N GYKDRHDMGQUZPU-MGHWNKPDSA-N 0.000 description 2
- JVYIGCARISMLMV-HOCLYGCPSA-N Val-Gly-Trp Chemical compound CC(C)[C@@H](C(=O)NCC(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N JVYIGCARISMLMV-HOCLYGCPSA-N 0.000 description 2
- APQIVBCUIUDSMB-OSUNSFLBSA-N Val-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](C(C)C)N APQIVBCUIUDSMB-OSUNSFLBSA-N 0.000 description 2
- UZQJVUCHXGYFLQ-AYDHOLPZSA-N [(2s,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-4-[(2r,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-3,5-dihydroxy-6-(hydroxymethyl)-4-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3,5-dihydroxy-6-(hy Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O)O[C@H]1CC[C@]2(C)[C@H]3CC=C4[C@@]([C@@]3(CC[C@H]2[C@@]1(C=O)C)C)(C)CC(O)[C@]1(CCC(CC14)(C)C)C(=O)O[C@H]1[C@@H]([C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O[C@H]4[C@@H]([C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)[C@H](O)[C@@H](CO)O4)O)[C@H](O)[C@@H](CO)O3)O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UZQJVUCHXGYFLQ-AYDHOLPZSA-N 0.000 description 2
- 108010093581 aspartyl-proline Proteins 0.000 description 2
- 108010092854 aspartyllysine Proteins 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- 238000002869 basic local alignment search tool Methods 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 206010014665 endocarditis Diseases 0.000 description 2
- 231100000776 exotoxin Toxicity 0.000 description 2
- 239000002095 exotoxin Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 108010020688 glycylhistidine Proteins 0.000 description 2
- 108010081551 glycylphenylalanine Proteins 0.000 description 2
- 108010053037 kyotorphin Proteins 0.000 description 2
- 108010047926 leucyl-lysyl-tyrosine Proteins 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 229920000656 polylysine Polymers 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 108010084932 tryptophyl-proline Proteins 0.000 description 2
- BUDNAJYVCUHLSV-ZLUOBGJFSA-N Ala-Asp-Ser Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(O)=O BUDNAJYVCUHLSV-ZLUOBGJFSA-N 0.000 description 1
- NJPMYXWVWQWCSR-ACZMJKKPSA-N Ala-Glu-Asn Chemical compound C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NJPMYXWVWQWCSR-ACZMJKKPSA-N 0.000 description 1
- BUQICHWNXBIBOG-LMVFSUKVSA-N Ala-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H](C)N BUQICHWNXBIBOG-LMVFSUKVSA-N 0.000 description 1
- RIPMDCIXRYWXSH-KNXALSJPSA-N Ala-Trp-Pro Chemical compound C[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N3CCC[C@@H]3C(=O)O)N RIPMDCIXRYWXSH-KNXALSJPSA-N 0.000 description 1
- 101710150620 Anionic peptide Proteins 0.000 description 1
- 206010053555 Arthritis bacterial Diseases 0.000 description 1
- RJUHZPRQRQLCFL-IMJSIDKUSA-N Asn-Asn Chemical compound NC(=O)C[C@H](N)C(=O)N[C@@H](CC(N)=O)C(O)=O RJUHZPRQRQLCFL-IMJSIDKUSA-N 0.000 description 1
- MQLZLIYPFDIDMZ-HAFWLYHUSA-N Asn-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H](N)CC(N)=O MQLZLIYPFDIDMZ-HAFWLYHUSA-N 0.000 description 1
- ACKNRKFVYUVWAC-ZPFDUUQYSA-N Asn-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)N)N ACKNRKFVYUVWAC-ZPFDUUQYSA-N 0.000 description 1
- QJMCHPGWFZZRID-BQBZGAKWSA-N Asn-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC(N)=O QJMCHPGWFZZRID-BQBZGAKWSA-N 0.000 description 1
- VBKIFHUVGLOJKT-FKZODXBYSA-N Asn-Thr Chemical compound C[C@@H]([C@@H](C(=O)O)NC(=O)[C@H](CC(=O)N)N)O VBKIFHUVGLOJKT-FKZODXBYSA-N 0.000 description 1
- RGGVDKVXLBOLNS-JQWIXIFHSA-N Asn-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CC(N)=O)N)C(O)=O)=CNC2=C1 RGGVDKVXLBOLNS-JQWIXIFHSA-N 0.000 description 1
- CYCKJEFVFNRWEZ-UGYAYLCHSA-N Asp-Ile-Asn Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(O)=O CYCKJEFVFNRWEZ-UGYAYLCHSA-N 0.000 description 1
- SEMWSADZTMJELF-BYULHYEWSA-N Asp-Ile-Gly Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(O)=O SEMWSADZTMJELF-BYULHYEWSA-N 0.000 description 1
- MRYDJCIIVRXVGG-QEJZJMRPSA-N Asp-Trp-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCC(O)=O)C(O)=O MRYDJCIIVRXVGG-QEJZJMRPSA-N 0.000 description 1
- NALWOULWGHTVDA-UWVGGRQHSA-N Asp-Tyr Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 NALWOULWGHTVDA-UWVGGRQHSA-N 0.000 description 1
- 208000034309 Bacterial disease carrier Diseases 0.000 description 1
- 206010006563 Bullous impetigo Diseases 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 206010016952 Food poisoning Diseases 0.000 description 1
- 208000019331 Foodborne disease Diseases 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- KGNSGRRALVIRGR-QWRGUYRKSA-N Gln-Tyr Chemical compound NC(=O)CC[C@H](N)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 KGNSGRRALVIRGR-QWRGUYRKSA-N 0.000 description 1
- TUTIHHSZKFBMHM-WHFBIAKZSA-N Glu-Asn Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(N)=O)C(O)=O TUTIHHSZKFBMHM-WHFBIAKZSA-N 0.000 description 1
- SBYVDRJAXWSXQL-AVGNSLFASA-N Glu-Asn-Phe Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O SBYVDRJAXWSXQL-AVGNSLFASA-N 0.000 description 1
- KOSRFJWDECSPRO-WDSKDSINSA-N Glu-Glu Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(O)=O KOSRFJWDECSPRO-WDSKDSINSA-N 0.000 description 1
- SITLTJHOQZFJGG-XPUUQOCRSA-N Glu-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H](N)CCC(O)=O SITLTJHOQZFJGG-XPUUQOCRSA-N 0.000 description 1
- BRFJMRSRMOMIMU-WHFBIAKZSA-N Gly-Ala-Asn Chemical compound NCC(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(O)=O BRFJMRSRMOMIMU-WHFBIAKZSA-N 0.000 description 1
- IKAIKUBBJHFNBZ-LURJTMIESA-N Gly-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)CN IKAIKUBBJHFNBZ-LURJTMIESA-N 0.000 description 1
- BCCRXDTUTZHDEU-VKHMYHEASA-N Gly-Ser Chemical compound NCC(=O)N[C@@H](CO)C(O)=O BCCRXDTUTZHDEU-VKHMYHEASA-N 0.000 description 1
- TVTZEOHWHUVYCG-KYNKHSRBSA-N Gly-Thr-Thr Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O TVTZEOHWHUVYCG-KYNKHSRBSA-N 0.000 description 1
- AJHCSUXXECOXOY-NSHDSACASA-N Gly-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)CN)C(O)=O)=CNC2=C1 AJHCSUXXECOXOY-NSHDSACASA-N 0.000 description 1
- 238000003794 Gram staining Methods 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- CKRFDMPBSWYOBT-PPCPHDFISA-N Ile-Lys-Thr Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)N CKRFDMPBSWYOBT-PPCPHDFISA-N 0.000 description 1
- DRCKHKZYDLJYFQ-YWIQKCBGSA-N Ile-Thr Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O DRCKHKZYDLJYFQ-YWIQKCBGSA-N 0.000 description 1
- 208000004575 Infectious Arthritis Diseases 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
- JYOAXOMPIXKMKK-YUMQZZPRSA-N Leu-Gln Chemical compound CC(C)C[C@H]([NH3+])C(=O)N[C@H](C([O-])=O)CCC(N)=O JYOAXOMPIXKMKK-YUMQZZPRSA-N 0.000 description 1
- XGDCYUQSFDQISZ-BQBZGAKWSA-N Leu-Ser Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(O)=O XGDCYUQSFDQISZ-BQBZGAKWSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- JPNRPAJITHRXRH-BQBZGAKWSA-N Lys-Asn Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CC(N)=O JPNRPAJITHRXRH-BQBZGAKWSA-N 0.000 description 1
- PBIPLDMFHAICIP-DCAQKATOSA-N Lys-Glu-Glu Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O PBIPLDMFHAICIP-DCAQKATOSA-N 0.000 description 1
- HGNRJCINZYHNOU-LURJTMIESA-N Lys-Gly Chemical compound NCCCC[C@H](N)C(=O)NCC(O)=O HGNRJCINZYHNOU-LURJTMIESA-N 0.000 description 1
- SBQDRNOLGSYHQA-YUMQZZPRSA-N Lys-Ser-Gly Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)NCC(O)=O SBQDRNOLGSYHQA-YUMQZZPRSA-N 0.000 description 1
- ZOKVLMBYDSIDKG-CSMHCCOUSA-N Lys-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](N)CCCCN ZOKVLMBYDSIDKG-CSMHCCOUSA-N 0.000 description 1
- UNPGTBHYKJOCCZ-DCAQKATOSA-N Met-Lys-Ala Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O UNPGTBHYKJOCCZ-DCAQKATOSA-N 0.000 description 1
- 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 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
- 206010031252 Osteomyelitis Diseases 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- PYOHODCEOHCZBM-RYUDHWBXSA-N Phe-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=CC=C1 PYOHODCEOHCZBM-RYUDHWBXSA-N 0.000 description 1
- GLEOIKLQBZNKJZ-WDSKDSINSA-N Pro-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1 GLEOIKLQBZNKJZ-WDSKDSINSA-N 0.000 description 1
- GVUVRRPYYDHHGK-VQVTYTSYSA-N Pro-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1 GVUVRRPYYDHHGK-VQVTYTSYSA-N 0.000 description 1
- 201000001177 Pyomyositis Diseases 0.000 description 1
- 208000021326 Ritter disease Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- SSJMZMUVNKEENT-IMJSIDKUSA-N Ser-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H](N)CO SSJMZMUVNKEENT-IMJSIDKUSA-N 0.000 description 1
- WOUIMBGNEUWXQG-VKHMYHEASA-N Ser-Gly Chemical compound OC[C@H](N)C(=O)NCC(O)=O WOUIMBGNEUWXQG-VKHMYHEASA-N 0.000 description 1
- GZFAWAQTEYDKII-YUMQZZPRSA-N Ser-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CO GZFAWAQTEYDKII-YUMQZZPRSA-N 0.000 description 1
- BXLYSRPHVMCOPS-ACZMJKKPSA-N Ser-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H](N)CO BXLYSRPHVMCOPS-ACZMJKKPSA-N 0.000 description 1
- LDEBVRIURYMKQS-WISUUJSJSA-N Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](N)CO LDEBVRIURYMKQS-WISUUJSJSA-N 0.000 description 1
- 206010040893 Skin necrosis Diseases 0.000 description 1
- 206010062255 Soft tissue infection Diseases 0.000 description 1
- 206010065769 Soft tissue necrosis Diseases 0.000 description 1
- 206010041929 Staphylococcal scalded skin syndrome Diseases 0.000 description 1
- BIYXEUAFGLTAEM-WUJLRWPWSA-N Thr-Gly Chemical compound C[C@@H](O)[C@H](N)C(=O)NCC(O)=O BIYXEUAFGLTAEM-WUJLRWPWSA-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
- PWIQCLSQVQBOQV-AAEUAGOBSA-N Trp-Glu Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(O)=O)=CNC2=C1 PWIQCLSQVQBOQV-AAEUAGOBSA-N 0.000 description 1
- YBRHKUNWEYBZGT-WLTAIBSBSA-N Trp-Thr Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H]([C@H](O)C)C(O)=O)=CNC2=C1 YBRHKUNWEYBZGT-WLTAIBSBSA-N 0.000 description 1
- QZOSVNLXLSNHQK-UWVGGRQHSA-N Tyr-Asp Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 QZOSVNLXLSNHQK-UWVGGRQHSA-N 0.000 description 1
- UBAQSAUDKMIEQZ-QWRGUYRKSA-N Tyr-Gln Chemical compound NC(=O)CC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 UBAQSAUDKMIEQZ-QWRGUYRKSA-N 0.000 description 1
- HPYDSVWYXXKHRD-VIFPVBQESA-N Tyr-Gly Chemical compound [O-]C(=O)CNC(=O)[C@@H]([NH3+])CC1=CC=C(O)C=C1 HPYDSVWYXXKHRD-VIFPVBQESA-N 0.000 description 1
- KYPMKDGKAYQCHO-RYUDHWBXSA-N Tyr-Met Chemical compound CSCC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 KYPMKDGKAYQCHO-RYUDHWBXSA-N 0.000 description 1
- ZSXJENBJGRHKIG-UWVGGRQHSA-N Tyr-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 ZSXJENBJGRHKIG-UWVGGRQHSA-N 0.000 description 1
- GVRKWABULJAONN-VQVTYTSYSA-N Val-Thr Chemical compound CC(C)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GVRKWABULJAONN-VQVTYTSYSA-N 0.000 description 1
- 108010059993 Vancomycin Proteins 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 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 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001147 anti-toxic effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000005875 antibody response Effects 0.000 description 1
- 108010068265 aspartyltyrosine Proteins 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 108091036078 conserved sequence Proteins 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 1
- 108010079547 glutamylmethionine Proteins 0.000 description 1
- 108010050848 glycylleucine Proteins 0.000 description 1
- 108010015792 glycyllysine Proteins 0.000 description 1
- 108010084389 glycyltryptophan Proteins 0.000 description 1
- 108060003552 hemocyanin Proteins 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 201000007119 infective endocarditis Diseases 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 208000015688 methicillin-resistant staphylococcus aureus infectious disease Diseases 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000002887 multiple sequence alignment Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- -1 neopenicillin Chemical compound 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000007918 pathogenicity Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 108010073101 phenylalanylleucine Proteins 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 201000001223 septic arthritis Diseases 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 206010040872 skin infection Diseases 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 229940125575 vaccine candidate Drugs 0.000 description 1
- 229940124856 vaccine component Drugs 0.000 description 1
- 229960003165 vancomycin Drugs 0.000 description 1
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 1
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/305—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Micrococcaceae (F)
- C07K14/31—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Micrococcaceae (F) from Staphylococcus (G)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- 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
-
- 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
- C07K14/76—Albumins
- C07K14/765—Serum albumin, e.g. HSA
-
- 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
- C07K14/78—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/795—Porphyrin- or corrin-ring-containing peptides
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G69/00—Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
- C08G69/02—Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids
- C08G69/36—Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids derived from amino acids, polyamines and polycarboxylic acids
-
- 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
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
- G01N33/56911—Bacteria
- G01N33/56938—Staphylococcus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- Cell Biology (AREA)
- Polymers & Plastics (AREA)
- Microbiology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Food Science & Technology (AREA)
- Virology (AREA)
- Analytical Chemistry (AREA)
- Biotechnology (AREA)
- Pathology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Peptides Or Proteins (AREA)
Abstract
本发明公开了本发明提供了一种用于诊断或防治金黄色葡萄球菌感染的抗原表位肽,包含氨基酸序列为SEQ ID NO:1的多肽,本发明还提供了该抗原表位肽在制备用于诊断、预防或治疗金黄色葡萄球菌感染中的应用。本发明通过筛选确定了金黄色葡萄球菌溶血素α的抗体优势表位肽,具有较强的免疫原性,同时该优势表位肽的氨基酸序列在多种S.aureus菌株中序列保守,因此,也可用于制备金黄色葡萄球菌感染的诊断试剂,或用于其他S.aureus感染的预防或治疗。
Description
技术领域
本发明涉及医疗诊断技术领域,具体涉一种用于诊断或防治金黄色葡萄球菌感染的抗原表位肽及其应用。
背景技术
金黄色葡萄球菌(Staphylococcus aureus,S.aureus)作为革兰氏阳性菌的代表,是一类在自然界广泛存在的致病性球菌,也是引起医院感染和社区感染的一种重要致病菌。调查研究表明,在美国,社区皮肤及软组织感染最常见的病原菌为S.aureus(约占75%);在日本,脓疱病中S.aureus引发的大疱性脓疱病占的92%;在非洲,热带脓性肌炎病原体中S.aureus占55-72%;在中国,感染性心内膜炎的头号致病菌为S.aureus(占31-34%)。此外,S.aureus感染以急性、化脓性为特征,局部可引起皮肤和软组织等的化脓性感染,经久不愈;全身可导致骨髓炎、脓毒性关节炎、心内膜炎、肺炎、脓毒血症等严重感染及并发症,死亡率高达20%。同时,金黄色葡萄球菌的外毒素还可引起食物中毒、烫伤样皮肤综合征和中毒性休克综合征等全身致死性感染。
对于金黄色葡萄球菌感染的治疗,通常选用红霉素、新型青霉素、庆大霉素、万古霉素或先锋霉素VI等抗生素。但是由于多重耐药金黄色葡萄球菌的出现,目前用单一抗生素治疗金黄色葡萄球菌感染已经越来越困难。临床数据显示,具有多重抗生素耐药性的金黄色葡萄球菌在社区金黄色葡萄球菌感染中占到60%,而在医院这一比例占到80%。其中特别突出的是甲氧西林耐药的金黄色葡萄球菌菌株(methicillin-resistant S.aureus,MRSA),2009年欧洲9个国家MRSA占到临床金黄色葡萄球菌株的25-50%。MRSA导致的感染用抗生素疗法难以治愈并且有很高的致死率。2018年中国MRSA全国平均检出率为35.0%,居革兰阳性耐药菌首位。MRSA侵袭性感染所致菌血症,90天内死亡率超过50%。目前临床主要的抗生素治疗已无力控制MRSA感染,疫苗研制迫在眉睫。
MRSA致病力强弱主要取决于其产生的毒素和侵袭酶的能力,其中溶血素α(alpha-Hemolysin,Hla)也是金葡菌感染致病的重要外毒素,通常由致病性金葡菌特别是MRSA产生,Hla可通过促使中性粒细胞裂解、损害上皮细胞,引起菌血症等临床症状,Hla免疫可缓解MRSA流行株所致的皮肤、软组织坏死及肺炎。通过Blast比对分析,Hla基因序列在已公布的致病性金黄色葡萄球菌中具有高度的保守性,其基因同源性大于90%,因此是理想的疫苗候选抗原。但由于Hla溶血活性强,直接作为疫苗组分可能存在安全性问题。研究证实,第35位的组氨酸(His)在穿孔复合物形成中具有重要作用,对该氨基酸进行定点突变为亮氨酸(Leu)后,可大大降低Hla的溶血活性。因此,本品中的Hla组分为经突变获得的突变子HlaH35L,除了降低溶血活性外未发现其他生物学功能改变。
在MRSA的疫苗应答中,抗体应答起主要保护作用。研究证实,不能产生抗毒素中和抗体的人更易发生葡萄球菌感染相关的毒性休克综合征。由于蛋白抗原发挥其功能主要通过表位来体现特异性。因此,Hla抗原中免疫优势应答的保护性表位的鉴定,是提升和优化基于Hla抗原的金黄色葡萄球菌疫苗设计的重要前提。筛选Hla的免疫优势表位,是激发更有效的Hla免疫应答的前提。目前的已知的Hla的B细胞表位,或通过生物信息学软件推测,或通过单克隆抗体鉴定,或使用人或动物免疫模型中鉴定,该方法均无法鉴定临床MRSA感染状态下的人群免疫优势表位。尚未有全面筛选临床MRSA感染状态,参与免疫应答的Hla的优势表位的报道。因此,建立一种准确有效的筛选及鉴定临床MRSA感染状态下,参与免疫应答的Hla的B细胞优势表位的方法显得尤为重要。
发明内容
本发明的目的是为了解决现有技术存在的上述问题,提供了一种金黄色葡萄球菌溶血素α的抗体优势表位肽,以及该表位肽在制备用于诊断、预防和/或治疗金黄色葡萄球菌感染的药物中的应用。
本发明提供了一种用于诊断或防治金黄色葡萄球菌感染的α溶血素抗原表位肽,包含氨基酸序列为SEQ ID NO:1(KVIFNNMVNQNW)的多肽。
在根据本发明的一个实施方案中,所述α溶血素抗原表位肽为氨基酸序列为SEQID NO:29或SEQ ID NO:30的多肽。
在根据本发明的一个实施方案中,还包含偶联在所述多肽N端或C端的多肽标记。
在根据本发明的一个实施方案中,所述多肽标记为生物素标记或荧光标记。
本发明还提供了一种用于制备抗金黄色葡萄球菌的抗体的融合蛋白,所述融合蛋白包含载体蛋白和上述的α溶血素抗原表位肽;所述载体蛋白选自匙孔血蓝蛋白(KLH)、牛血清白蛋(BSA)、甲状腺球蛋白、纤维蛋白原、明胶、多聚抗原肽中的一种;优选地,所述多聚抗原肽为多聚赖氨酸(PLL)。
本发明还提供了上述α溶血素抗原表位肽在制备用于诊断、预防或治疗金黄色葡萄球菌感染的药物中的应用。所述金黄色葡萄球菌可以为任意的能够引起感染的金黄色葡萄球菌,特别是耐药性极强的甲氧西林耐药的金黄色葡萄球菌菌株,所述甲氧西林耐药的金黄色葡萄球菌菌株可以为MRSA252标准株。
本发明进一步提供了一种用于金黄色葡萄球菌感染的诊断试剂,包含上述的抗原表位肽。
在根据本发明的一个实施方案中所述α溶血素抗原表位肽,包被于检测载体上,所述检测载体选自聚苯乙烯微量反应板、胶体金试剂条、磁珠和微流控芯片中的任一种。
在根据本发明的一个实施方案中,还包含特异性识别人IgG抗体的第二抗体;例如,用免疫优势表位肽—KLH(钥孔血蓝蛋白)偶联物融合蛋白免疫动物,分析该优势表位肽的免疫原性与免疫反应性。
优选地,所述第二抗体选自兔抗人单克隆抗体、兔抗人多克隆抗体、鼠抗人单克隆抗体、鼠抗人多克隆抗体、羊抗人多克隆抗体或羊抗人多克隆抗体中的一种;
优选地,所述第二抗体偶联有激活或猝灭所述特异性荧光基团的配合基团。
本发明的另一方面提供了上述的抗原表位肽在制备用于预防和/或治疗金黄色葡萄球菌感染的药物中的应用。所述药物可以被制备成不同的剂型而通过不同的途径进行给药,优选的,为了避免所述疫苗中抗原成分的降解,所述疫苗被制备成用于静脉给药的剂型,例如,可以为针剂。
本发明进一步提供了一种用于预防或治疗金黄色葡萄球菌感染的药物,其包含上述的α溶血素抗原表位肽。
在根据本发明的一个实施方案中,所述佐剂选自Quil-A佐剂(购自InvivoGen公司)
本发明的有益效果是:
本发明提供的金黄色葡萄球菌溶血素α的抗体优势表位肽均能在动物体内诱发高水平优势表位抗血清,可以用于制备预防金黄色葡萄球菌感染的高效、低毒、高安全性的基于Hla的药物,如预防型疫苗。
本发明提供的金黄色葡萄球菌溶血素α的抗体优势表位肽具有较强的免疫原性,用该优势表位免疫动物,免疫制剂无无关成分或有害成分,以该优势表位肽制备的特异性单克隆抗体可以较好地的预防金黄色葡萄球菌感染。
经序列比对分析,本发明提供的金黄色葡萄球菌溶血素α的抗体优势表位肽在多种S.aureus菌株中序列保守,因此,其也可用作金黄色葡萄球菌感染的诊断试剂或用于对其他S.aureus感染的预防和治疗。
附图说明
图1为使用人群的MRSA阳性抗血清作为一抗对本发明筛选到的重叠肽进行ELISA检测的结果图谱;
图2为本发明筛选到的免疫优势表位肽免疫小鼠获得的抗血清与Hla表位肽的结合能力分析结果图谱;
图3为本发明筛选到的免疫优势表位肽Hla162-179、Hla168-185的KLH融合蛋白经主动免疫减轻小鼠肾脏及肺脏金黄色葡萄球菌的定植的能力检测图谱;
图4为本发明筛选到的抗体免疫优势表位肽Hla162-179、Hla168-185在Hla三维结构中的位置分布分析结果图谱;
图5为本发明筛选到的抗体免疫优势表位肽Hla162-179、Hla168-185的氨基酸序列保守性分析结果图谱。
具体实施方式
下面对本发明的较佳实施例进行详细阐述,以使本发明的优点和特征能更易被本领域人员理解,从而对本发明的保护范围做出更为清楚明确的界定。
下述实施例中所使用的实验方法如无特殊说明,均为常规方法。下述实施例中所用的材料、试剂等,如无特殊说明,均可从商业途径得到。
实施例1重叠肽的获得
以Hla蛋白序列(Sequence ID:ADQ77533.1)为基础,相对于预期的重叠肽的长度,每次向下游移动小于重叠肽的长度的氨基酸个数,再次获得另一条预期的重叠肽。其中,预期的重叠肽的长度可以为15-30个氨基酸,每次步移的氨基酸个数可以为4-8个,本实施例中从第1号氨基酸开始,每次步移6个氨基酸,合成步移重叠的18个氨基酸多肽(上海强耀生物科技有限公司),共得到47条重叠肽。纯度均大于95%。合成的步移重叠肽信息如表1所示。将合成肽段用二甲亚砜(DMSO)溶解至1mg/mL的储存浓度,分装后-70℃冻存,临用时用PBS稀释成1mM。
表1步移重叠肽
实施例2临床MRSA阳性血清的收集和保存
用临床签署知情同意书的MRSA阳性血清人群(25位18-64岁金葡菌感染者)测抗血清效价,选择Hla效价大于1:64000的临床MRSA阳性血清用于后续检测。
实施例3 Hla的B细胞免疫优势表位的筛选
调整重叠肽包被浓度15μg/孔(以全蛋白Hla(Sequence ID:ADQ77533.1)为阳性对照),对孔板进行包被-洗涤-封闭-再次洗涤后,加入实施例2获得的Hla免疫抗血清,稀释度为1∶300,孵育1.5h-洗涤后,加入HRP-羊抗小鼠IgG(购自恩晶生物,货号E1WP319),稀释度为1∶3500,洗涤后加入TMB底物显色液(购自Beyotime/碧云天,货号P0209-100ml),终止反应后在450nm处读OD值,按照公式18氨基酸重叠肽OD检测值-空白对照检测值)/(阴性肽OD检测值-空白对照检测值)≥2.1为阳性重叠肽。经SPSS16.0数据检验,获得相对于其他阳性重叠肽读数具有显著统计学意义的阳性重叠肽,定义为B细胞的免疫优势表位肽,也即免疫优势表位肽。
结果如图1所示:有2个阳性重叠肽Hla162-179(SEQ ID NO:29DKKVGWKVIFNNMVNQNW)、Hla168-185(SEQ ID NO:30 KVIFNNMVNQNWGPYDRD),与其他优势表位肽读数具有显著统计学意义,定义为免疫优势表位,该图中OVA192-201为阴性无关肽。该方法不仅筛选出了Hla的所有免疫应答的B细胞表位,而且明确了Hla的B细胞免疫优势表位肽。
实施例4 Hla的优势表位肽的免疫原性及免疫反应性鉴定
将实施例3鉴定到的Hla的B细胞免疫优势表位肽与KLH(血蓝蛋白)等浓度偶联(委托上海吉尔生化有限公司完成),得到融合蛋白,表位肽-KLH融合蛋白以60μg/只,Quil-A佐剂(购自InvivoGen公司)剂量以10ug/只,混合后于0、14、21天经BALB/c小鼠(10只,6-8周龄)大腿肌注免疫,末次免疫7天后取小鼠眼球血,分离抗血清,测抗血清效价,分装后-70℃冻存。
抗血清与优势表位肽的结合的检测:调整Hla优势表位肽包被浓度为15μg/孔,包被-洗涤-封闭-再次洗涤后,加入稀释度分别为1∶50,1∶100,1∶200,1∶400,1∶800,1∶1600,1∶3200,1∶6400,1∶12800,1∶25600及1∶51200的抗血清(正常小鼠血清作阴性对照,PBS为空白对照),孵育1.5h-洗涤后,加入HRP-羊抗小鼠IgG(购自恩晶生物,货号E1WP319),的稀释度为1∶3500,洗涤后加入TMB底物显色液购自Beyotime/碧云天,货号P0209-100ml),终止反应后在450nm处读OD值。
结果如图2所示:Anti-Hla162-179-KLH免疫小鼠的优势表位肽的抗血清平均效价为1:22400,Anti-Hla168-185-KLH免疫小鼠的优势表位肽的抗血清平均效价分别为1:12800。以抗血清稀释度为横坐标,以450nm处OD值为纵坐标,可见Hla优势表位肽特异性抗血清在对应效价时,均能较强地与Hla表位肽结合。
实施例5免疫优势表位肽主动免疫减轻小鼠肾脏及肺脏金黄色葡萄球菌的定植的能力检测
免疫优势表位肽-KLH融合蛋白在Qui-A佐剂(购自)辅助下于第0,14,21天经三次肌注免疫6-8周BALB/c小鼠,末次免疫后第7天,尾静脉注射亚致死剂量MRSA252标准株(购自ATCC美国模式培养物菌种资源库,6×108CFU/ml)感染小鼠。在攻毒的第48小时,采集小鼠肾脏及肺脏组织,检测每只小鼠脏器细菌定植数量,评价该优势表位肽特异性单克隆抗体对小鼠的主动免疫保护效果。同时,设置PBS未主动免疫对照组。金黄色葡萄球菌定植量的检测:脱颈椎处死BALB/c小鼠,75%酒精消毒,无菌取组织标本称重,置于2ml无菌的PBS中,于洁净的玻璃匀浆器中进行匀浆,取1ml均浆按照1∶10,1∶100,1∶1000比例进行稀释,每稀释度各取100μL轻轻涂布于固体培养基上,置于37℃,培养24h,做菌落计数(CFU/ml),并行革兰氏染色典型的镜下形态和PCR检测以证实为金黄色葡萄球菌。
结果如图3所示,结果显示:与PBS组为对照,Hla168-185-KLH主动免疫能显著减轻小鼠肾脏和肺脏的MRSA252定植数量,P值有统计学差异(*表示P<0.05,**表示P<0.001)。而Hla162-179-KLH主动免疫并未获得显著的清除脏器细菌的效果。证实,Hla168-185为抗MRSA252标准菌株感染的保护性免疫优势表位。
实施例6
本实施例用于说明抗体免疫优势表位肽在Hla全蛋白三维结构中的位置分布分析结果
在PubMed蛋白公开数据库下载已报道Hla蛋白的3D结构图,用PyMOL 1.1 program软件标注实验中筛选出的免疫优势表位肽的序列位置。
结果如图4所示,该优势肽Hla162-179、Hla168-185分别位于Hla三维晶体结构的β片层和loop区,可见,该优势表位肽序列(抗体优势表位)是Hla表位疫苗的可靠候选分子。
实施例7
本实施例用于本发明筛选到的抗体免疫优势表位肽Hla162-179、Hla168-185的氨基酸序列保守性分析结果。
在Genbank数据库检索36株金黄色葡萄球菌的Hla蛋白的氨基酸序列,用NCBI的Basic Local Alignment Search Tool(BLAST)软件进行氨基酸序列比对分析,随机选择36株菌株进行多序列比对(Multiple Alignment),网站地址为https://blast.ncbi.nlm.nih.gov/Blast.cgi。
结果如图5所示,该优势肽Hla162-179、Hla168-185在36种金黄色葡萄球菌各菌株中的氨基酸序列保守,因此具有良好的应用前景。
上述发明内容及具体实施方式意在证明本发明所提供技术方案的实际应用,不应解释为对本发明保护范围的限定。本领域技术人员在本发明的精神和原理内,当可作各种修改、等同替换、或改进。本发明的保护范围以所附权利要求书为准。
序列表
<110> 中国人民解放军陆军军医大学
<120> 一种用于诊断或防治金黄色葡萄球菌感染的α溶血素抗原表位肽及其应用
<141> 2021-02-05
<160> 48
<170> SIPOSequenceListing 1.0
<210> 1
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 1
Lys Val Ile Phe Asn Asn Met Val Asn Gln Asn Trp Gly Pro Tyr Asp
1 5 10 15
Arg Asp
<210> 2
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 2
Ala Asp Ser Asp Ile Asn Ile Lys Thr Gly Thr Thr Asp Ile Gly Ser
1 5 10 15
Asn Thr
<210> 3
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 3
Asn Ile Lys Thr Gly Thr Thr Asp Ile Gly Ser Asn Thr Thr Val Lys
1 5 10 15
Thr Gly
<210> 4
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 4
Thr Asp Ile Gly Ser Asn Thr Thr Val Lys Thr Gly Asp Leu Val Thr
1 5 10 15
Tyr Asp
<210> 5
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 5
Thr Thr Val Lys Thr Gly Asp Leu Val Thr Tyr Asp Lys Glu Asn Gly
1 5 10 15
Met Leu
<210> 6
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 6
Asp Leu Val Thr Tyr Asp Lys Glu Asn Gly Met Leu Lys Lys Val Phe
1 5 10 15
Tyr Ser
<210> 7
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 7
Lys Glu Asn Gly Met Leu Lys Lys Val Phe Tyr Ser Phe Ile Asp Asp
1 5 10 15
Lys Asn
<210> 8
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 8
Lys Lys Val Phe Tyr Ser Phe Ile Asp Asp Lys Asn His Asn Lys Lys
1 5 10 15
Ile Leu
<210> 9
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 9
Phe Ile Asp Asp Lys Asn His Asn Lys Lys Ile Leu Val Ile Arg Thr
1 5 10 15
Lys Gly
<210> 10
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 10
His Asn Lys Lys Ile Leu Val Ile Arg Thr Lys Gly Thr Ile Ala Gly
1 5 10 15
Gln Tyr
<210> 11
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 11
Val Ile Arg Thr Lys Gly Thr Ile Ala Gly Gln Tyr Arg Val Tyr Ser
1 5 10 15
Glu Glu
<210> 12
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 12
Thr Ile Ala Gly Gln Tyr Arg Val Tyr Ser Glu Glu Gly Ala Asn Lys
1 5 10 15
Ser Gly
<210> 13
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 13
Arg Val Tyr Ser Glu Glu Gly Ala Asn Lys Ser Gly Leu Ala Trp Pro
1 5 10 15
Ser Ala
<210> 14
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 14
Gly Ala Asn Lys Ser Gly Leu Ala Trp Pro Ser Ala Phe Lys Val Gln
1 5 10 15
Leu Gln
<210> 15
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 15
Leu Ala Trp Pro Ser Ala Phe Lys Val Gln Leu Gln Leu Pro Asp Asn
1 5 10 15
Glu Val
<210> 16
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 16
Phe Lys Val Gln Leu Gln Leu Pro Asp Asn Glu Val Ala Gln Ile Ser
1 5 10 15
Asp Tyr
<210> 17
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 17
Leu Pro Asp Asn Glu Val Ala Gln Ile Ser Asp Tyr Tyr Pro Arg Asn
1 5 10 15
Ser Ile
<210> 18
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 18
Ala Gln Ile Ser Asp Tyr Tyr Pro Arg Asn Ser Ile Asp Thr Lys Glu
1 5 10 15
Tyr Met
<210> 19
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 19
Tyr Pro Arg Asn Ser Ile Asp Thr Lys Glu Tyr Met Ser Thr Leu Thr
1 5 10 15
Tyr Gly
<210> 20
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 20
Asp Thr Lys Glu Tyr Met Ser Thr Leu Thr Tyr Gly Phe Asn Gly Asn
1 5 10 15
Val Thr
<210> 21
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 21
Ser Thr Leu Thr Tyr Gly Phe Asn Gly Asn Val Thr Gly Asp Asp Ser
1 5 10 15
Gly Lys
<210> 22
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 22
Phe Asn Gly Asn Val Thr Gly Asp Asp Ser Gly Lys Ile Gly Gly Leu
1 5 10 15
Ile Gly
<210> 23
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 23
Gly Asp Asp Ser Gly Lys Ile Gly Gly Leu Ile Gly Ala Asn Val Ser
1 5 10 15
Ile Gly
<210> 24
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 24
Ile Gly Gly Leu Ile Gly Ala Asn Val Ser Ile Gly His Thr Leu Lys
1 5 10 15
Tyr Val
<210> 25
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 25
Ala Asn Val Ser Ile Gly His Thr Leu Lys Tyr Val Gln Pro Asp Phe
1 5 10 15
Lys Thr
<210> 26
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 26
His Thr Leu Lys Tyr Val Gln Pro Asp Phe Lys Thr Ile Leu Glu Ser
1 5 10 15
Pro Thr
<210> 27
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 27
Gln Pro Asp Phe Lys Thr Ile Leu Glu Ser Pro Thr Asp Lys Lys Val
1 5 10 15
Gly Trp
<210> 28
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 28
Ile Leu Glu Ser Pro Thr Asp Lys Lys Val Gly Trp Lys Val Ile Phe
1 5 10 15
Asn Asn
<210> 29
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 29
Asp Lys Lys Val Gly Trp Lys Val Ile Phe Asn Asn Met Val Asn Gln
1 5 10 15
Asn Trp
<210> 30
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 30
Lys Val Ile Phe Asn Asn Met Val Asn Gln Asn Trp Gly Pro Tyr Asp
1 5 10 15
Arg Asp
<210> 31
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 31
Met Val Asn Gln Asn Trp Gly Pro Tyr Asp Arg Asp Ser Trp Asn Pro
1 5 10 15
Val Tyr
<210> 32
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 32
Gly Pro Tyr Asp Arg Asp Ser Trp Asn Pro Val Tyr Gly Asn Gln Leu
1 5 10 15
Phe Met
<210> 33
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 33
Ser Trp Asn Pro Val Tyr Gly Asn Gln Leu Phe Met Lys Thr Arg Asn
1 5 10 15
Gly Ser
<210> 34
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 34
Gly Asn Gln Leu Phe Met Lys Thr Arg Asn Gly Ser Met Lys Ala Ala
1 5 10 15
Glu Asn
<210> 35
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 35
Lys Thr Arg Asn Gly Ser Met Lys Ala Ala Glu Asn Phe Leu Asp Pro
1 5 10 15
Asn Lys
<210> 36
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 36
Met Lys Ala Ala Glu Asn Phe Leu Asp Pro Asn Lys Ala Ser Ser Leu
1 5 10 15
Leu Ser
<210> 37
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 37
Phe Leu Asp Pro Asn Lys Ala Ser Ser Leu Leu Ser Ser Gly Phe Ser
1 5 10 15
Pro Asp
<210> 38
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 38
Ala Ser Ser Leu Leu Ser Ser Gly Phe Ser Pro Asp Phe Ala Thr Val
1 5 10 15
Ile Thr
<210> 39
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 39
Ser Gly Phe Ser Pro Asp Phe Ala Thr Val Ile Thr Met Asp Arg Lys
1 5 10 15
Ala Thr
<210> 40
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 40
Phe Ala Thr Val Ile Thr Met Asp Arg Lys Ala Thr Lys Gln Gln Thr
1 5 10 15
Asn Ile
<210> 41
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 41
Met Asp Arg Lys Ala Thr Lys Gln Gln Thr Asn Ile Asp Val Ile Tyr
1 5 10 15
Glu Arg
<210> 42
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 42
Lys Gln Gln Thr Asn Ile Asp Val Ile Tyr Glu Arg Val Arg Asp Asp
1 5 10 15
Tyr Gln
<210> 43
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 43
Asp Val Ile Tyr Glu Arg Val Arg Asp Asp Tyr Gln Leu His Trp Thr
1 5 10 15
Ser Thr
<210> 44
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 44
Val Arg Asp Asp Tyr Gln Leu His Trp Thr Ser Thr Asn Trp Lys Gly
1 5 10 15
Thr Asn
<210> 45
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 45
Leu His Trp Thr Ser Thr Asn Trp Lys Gly Thr Asn Thr Lys Asp Lys
1 5 10 15
Trp Thr
<210> 46
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 46
Asn Trp Lys Gly Thr Asn Thr Lys Asp Lys Trp Thr Asp Arg Ser Ser
1 5 10 15
Glu Arg
<210> 47
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 47
Thr Lys Asp Lys Trp Thr Asp Arg Ser Ser Glu Arg Tyr Lys Ile Asp
1 5 10 15
Trp Glu
<210> 48
<211> 18
<212> PRT
<213> 金黄色葡萄球菌(Staphylococcus aureus)
<400> 48
Asp Arg Ser Ser Glu Arg Tyr Lys Ile Asp Trp Glu Lys Glu Glu Met
1 5 10 15
Thr Asn
Claims (12)
1.一种用于诊断或防治金黄色葡萄球菌感染的α溶血素抗原表位肽,其特征在于,包含氨基酸序列为SEQ ID NO:1的多肽。
2.如权利要求1所述的α溶血素抗原表位肽,其特征在于,所述抗原表位肽为氨基酸序列为SEQ ID NO:29或SEQ ID NO:30的多肽。
3.如权利要求1或2所述的α溶血素抗原表位肽,其特征在于,还包含偶联在所述多肽N端或C端的多肽标记;优选地,所述多肽标记为生物素标记或荧光标记。
4.一种用于制备抗金黄色葡萄球菌的抗体的融合蛋白,其特征在于,所述融合蛋白包含如权利要求1或2所述的α溶血素抗原表位肽和载体蛋白;所述载体蛋白选自匙孔血蓝蛋白(KLH)、牛血清白蛋(BSA)、甲状腺球蛋白、纤维蛋白原、明胶或多聚抗原肽中的一种。
5.如权利要求1-3中任一项所述的α溶血素抗原表位肽在制备用于诊断、预防或治疗金黄色葡萄球菌感染的药物中的应用。
6.一种用于金黄色葡萄球菌感染的诊断试剂,其特征在于,包含如权利要求1-4中任一项所述的α溶血素抗原表位肽。
7.如权利要求6所述的诊断试剂,其特征在于,所述α溶血素抗原表位肽包被于检测载体上,所述检测载体选自聚苯乙烯微量反应板、胶体金试剂条、磁珠和微流控芯片中的任一种。
8.如权利要求7所述诊断试剂,其特征在于,还包含特异性识别人IgG抗体的第二抗体;
优选地,所述第二抗体选自兔抗人单克隆抗体、兔抗人多克隆抗体、鼠抗人单克隆抗体、鼠抗人多克隆抗体、羊抗人多克隆抗体或羊抗人多克隆抗体中的一种;
优选地,所述第二抗体偶联有激活或猝灭所述特异性荧光基团的配合基团。
9.如权利要求1或2所述的α溶血素抗原表位肽在制备用于预防和/或治疗金黄色葡萄球菌感染的药物中的应用。
10.一种用于预防或治疗金黄色葡萄球菌感染的药物,其特征在于,包含如权利要求1或2所述的α溶血素抗原表位肽和药学上可接受的辅料。
11.如权利要求10所述的药物,其特征在于,还包含药学上可接受的佐剂。
12.如权利要求11所述的药物,其特征在于,所述佐剂为Quil-A佐剂。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110163653.1A CN112851770B (zh) | 2021-02-05 | 2021-02-05 | 一种用于诊断或防治金黄色葡萄球菌感染的α溶血素抗原表位肽及其应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202110163653.1A CN112851770B (zh) | 2021-02-05 | 2021-02-05 | 一种用于诊断或防治金黄色葡萄球菌感染的α溶血素抗原表位肽及其应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN112851770A true CN112851770A (zh) | 2021-05-28 |
CN112851770B CN112851770B (zh) | 2022-10-04 |
Family
ID=75989294
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202110163653.1A Active CN112851770B (zh) | 2021-02-05 | 2021-02-05 | 一种用于诊断或防治金黄色葡萄球菌感染的α溶血素抗原表位肽及其应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN112851770B (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114685628A (zh) * | 2022-03-24 | 2022-07-01 | 中国人民解放军陆军军医大学 | 一种SARS-CoV-2的RBD的抗原表位肽及其应用 |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101951948A (zh) * | 2007-08-31 | 2011-01-19 | 芝加哥大学 | 与针对葡萄球菌性肺部疾病和病症进行免疫相关的方法和组合物 |
CN102647999A (zh) * | 2009-04-14 | 2012-08-22 | 诺华有限公司 | 用于免疫接种以抵御金黄色葡萄球菌的组合物 |
CN102977214A (zh) * | 2012-09-29 | 2013-03-20 | 重庆原伦生物科技有限公司 | 用于耐甲氧西林金黄色葡萄球菌(mrsa)疫苗的重组蛋白hf2及制备方法和应用 |
WO2013040142A2 (en) * | 2011-09-16 | 2013-03-21 | Iogenetics, Llc | Bioinformatic processes for determination of peptide binding |
US20130189249A1 (en) * | 2007-08-31 | 2013-07-25 | University Of Chicago | Methods and compositions related to immunizing against staphylococcal lung diseases and conditions |
CN103717234A (zh) * | 2011-06-19 | 2014-04-09 | 纽约大学 | 治疗和预防金黄色葡萄球菌感染及相关病状的方法 |
WO2014067912A1 (en) * | 2012-10-29 | 2014-05-08 | Novartis Ag | Staphylococcus aureus sdre cnab domain and its use for vaccination |
WO2018183475A1 (en) * | 2017-03-28 | 2018-10-04 | Children's Medical Center Corporation | A multiple antigen presenting system (maps)-based staphylococcus aureus vaccine, immunogenic composition, and uses thereof |
-
2021
- 2021-02-05 CN CN202110163653.1A patent/CN112851770B/zh active Active
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101951948A (zh) * | 2007-08-31 | 2011-01-19 | 芝加哥大学 | 与针对葡萄球菌性肺部疾病和病症进行免疫相关的方法和组合物 |
US20130189249A1 (en) * | 2007-08-31 | 2013-07-25 | University Of Chicago | Methods and compositions related to immunizing against staphylococcal lung diseases and conditions |
CN102647999A (zh) * | 2009-04-14 | 2012-08-22 | 诺华有限公司 | 用于免疫接种以抵御金黄色葡萄球菌的组合物 |
CN103717234A (zh) * | 2011-06-19 | 2014-04-09 | 纽约大学 | 治疗和预防金黄色葡萄球菌感染及相关病状的方法 |
WO2013040142A2 (en) * | 2011-09-16 | 2013-03-21 | Iogenetics, Llc | Bioinformatic processes for determination of peptide binding |
CN102977214A (zh) * | 2012-09-29 | 2013-03-20 | 重庆原伦生物科技有限公司 | 用于耐甲氧西林金黄色葡萄球菌(mrsa)疫苗的重组蛋白hf2及制备方法和应用 |
WO2014067912A1 (en) * | 2012-10-29 | 2014-05-08 | Novartis Ag | Staphylococcus aureus sdre cnab domain and its use for vaccination |
WO2018183475A1 (en) * | 2017-03-28 | 2018-10-04 | Children's Medical Center Corporation | A multiple antigen presenting system (maps)-based staphylococcus aureus vaccine, immunogenic composition, and uses thereof |
Non-Patent Citations (6)
Title |
---|
C. TKACZYK等: "Alanine Scanning Mutagenesis of the MEDI4893 (Suvratoxumab) Epitope Reduces Alpha Toxin Lytic Activity In Vitro and Staphylococcus aureus Fitness in Infection Models", 《ANTIMICROBIAL AGENTS AND CHEMOTHERAPY》 * |
JASON A. JOYNER等: "Vaccination with VLPs Presenting a Linear Neutralizing Domain of S. aureus Hla Elicits Protective Immunity", 《TOXINS》 * |
NASIM HAJIGHAHRAMANI等: "Immunoinformatics analysis and in silico designing of a novel multi-epitope peptide vaccine against Staphylococcus aureus", 《INFECTION, GENETICS AND EVOLUTION》 * |
张海燕 等: "金黄色葡萄球菌A-溶血素亚单位疫苗在小白鼠模型的免疫效力评价", 《中国生物工程杂志》 * |
陈益国: "金葡菌肽聚糖模拟肽疫苗候选保护性作用的初步研究", 《中国博士学位论文全文数据库(电子期刊)医药卫生科技辑》 * |
韦金佞: "基于金葡菌疫苗免疫后人体血清鉴定 Hla 抗原中和表位及其应用初步研究", 《中国优秀硕士学位论文全文数据库(电子期刊)医药卫生科技辑》 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114685628A (zh) * | 2022-03-24 | 2022-07-01 | 中国人民解放军陆军军医大学 | 一种SARS-CoV-2的RBD的抗原表位肽及其应用 |
CN114685628B (zh) * | 2022-03-24 | 2023-06-06 | 中国人民解放军陆军军医大学 | 一种SARS-CoV-2的RBD的抗原表位肽及其应用 |
Also Published As
Publication number | Publication date |
---|---|
CN112851770B (zh) | 2022-10-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5740714B2 (ja) | クロストリジウム・ディフィシル(Clostridiumdifficile)毒素に対する抗体 | |
EP1280828B1 (en) | Anthrax-specific antigen, vaccines comprising said antigen, anthrax-specific antibodies, and their uses | |
AU2016201992B2 (en) | Polypeptides and immunizing compositions containing gram positive polypeptides and methods of use | |
JP2012515551A5 (zh) | ||
Li et al. | The non-conserved region of MRP is involved in the virulence of Streptococcus suis serotype 2 | |
CN112851770B (zh) | 一种用于诊断或防治金黄色葡萄球菌感染的α溶血素抗原表位肽及其应用 | |
MX2010010614A (es) | Composiciones, metodos y kits. | |
CN113462675B (zh) | 一种ApuA蛋白抗原多肽及应用 | |
AU2010234193B2 (en) | Methods and compositions for treating and preventing Shiga toxin-producing Escherichia coli infection | |
CN112920259A (zh) | 一种用于诊断或防治金黄色葡萄球菌感染的IsdB抗原表位肽及其应用 | |
US20090162369A1 (en) | Synthetic chimeric peptides | |
US20140341895A1 (en) | PSEUDOMONAS AERUGINOSA OprM EPITOPES FOR USE IN DIAGNOSTICS AND THERAPEUTICS | |
RU2387715C2 (ru) | РЕКОМБИНАНТНЫЕ ДНК, ОБЕСПЕЧИВАЮЩИЕ ПОЛУЧЕНИЕ ПОЛИПЕПТИДОВ Р6, Р7, Р8, ОБЛАДАЮЩИХ ПРОТЕКТИВНЫМИ СВОЙСТВАМИ В ОТНОШЕНИИ STREPTOCOCCUS AGALACTIAE И СЕЛЕКТИВНО-СВЯЗЫВАЮЩИХ IgA | |
Ma et al. | A novel monoclonal antibody against FbaA can inhibit the binding of the complement regulatory protein factor H to group A streptococcus | |
US11801292B2 (en) | Polypeptide epitopes of S. aureus and respective monoclonal antibodies for the treatment of infections and immune-diagnosis | |
US20130004539A1 (en) | Methods for preventing and treating staphylococcus aureus colonization, infection, and disease | |
Ding et al. | Immunogenicity of a divalent group A streptococcal vaccine | |
AU2010229498B2 (en) | Polypeptides and immunizing compositions containing gram positive polypeptides and methods of use | |
CN115925906A (zh) | 抗新型冠状病毒核蛋白的单克隆抗体及其应用 | |
US20170014501A1 (en) | Methods for preventing and treating staphylococcus aureus colonization, infection, and disease | |
JP2004321010A (ja) | 新規レンサ球菌タンパク質抗原 | |
WO2013184900A2 (en) | Immunogenic compositions and related methods |
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 | ||
GR01 | Patent grant | ||
GR01 | Patent grant |