JP6646537B2 - オリゴ糖によるタンパク質の修飾及び標識方法 - Google Patents
オリゴ糖によるタンパク質の修飾及び標識方法 Download PDFInfo
- Publication number
- JP6646537B2 JP6646537B2 JP2016129992A JP2016129992A JP6646537B2 JP 6646537 B2 JP6646537 B2 JP 6646537B2 JP 2016129992 A JP2016129992 A JP 2016129992A JP 2016129992 A JP2016129992 A JP 2016129992A JP 6646537 B2 JP6646537 B2 JP 6646537B2
- Authority
- JP
- Japan
- Prior art keywords
- protein
- antibody
- glcnac
- oligosaccharide
- sugar
- 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.)
- Active
Links
- 108090000623 proteins and genes Proteins 0.000 title claims description 168
- 102000004169 proteins and genes Human genes 0.000 title claims description 165
- 229920001542 oligosaccharide Polymers 0.000 title claims description 123
- 150000002482 oligosaccharides Chemical class 0.000 title claims description 120
- 238000002372 labelling Methods 0.000 title description 53
- 230000004048 modification Effects 0.000 title description 10
- 238000012986 modification Methods 0.000 title description 10
- 238000000034 method Methods 0.000 claims description 84
- 210000004027 cell Anatomy 0.000 claims description 76
- 235000000346 sugar Nutrition 0.000 claims description 73
- 239000000126 substance Substances 0.000 claims description 61
- 102000004190 Enzymes Human genes 0.000 claims description 57
- 108090000790 Enzymes Proteins 0.000 claims description 57
- 150000001345 alkine derivatives Chemical class 0.000 claims description 49
- 239000007787 solid Substances 0.000 claims description 47
- 239000000758 substrate Substances 0.000 claims description 47
- -1 succinimidyl ester Chemical class 0.000 claims description 44
- 238000009739 binding Methods 0.000 claims description 39
- 230000027455 binding Effects 0.000 claims description 38
- OVRNDRQMDRJTHS-RTRLPJTCSA-N N-acetyl-D-glucosamine Chemical group CC(=O)N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-RTRLPJTCSA-N 0.000 claims description 37
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 35
- 239000002738 chelating agent Substances 0.000 claims description 34
- 108010031186 Glycoside Hydrolases Proteins 0.000 claims description 18
- 102000005744 Glycoside Hydrolases Human genes 0.000 claims description 18
- 238000003776 cleavage reaction Methods 0.000 claims description 18
- 230000007017 scission Effects 0.000 claims description 18
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 claims description 17
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 claims description 17
- 125000002355 alkine group Chemical group 0.000 claims description 16
- 230000001225 therapeutic effect Effects 0.000 claims description 16
- 101000895926 Streptomyces plicatus Endo-beta-N-acetylglucosaminidase H Proteins 0.000 claims description 13
- 239000002184 metal Substances 0.000 claims description 11
- 229910052751 metal Inorganic materials 0.000 claims description 11
- 108091005804 Peptidases Proteins 0.000 claims description 9
- 239000004365 Protease Substances 0.000 claims description 9
- 239000007850 fluorescent dye Substances 0.000 claims description 9
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 7
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 claims description 6
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 claims description 6
- 102000030902 Galactosyltransferase Human genes 0.000 claims description 6
- 108060003306 Galactosyltransferase Proteins 0.000 claims description 6
- 235000012538 ammonium bicarbonate Nutrition 0.000 claims description 6
- 239000001099 ammonium carbonate Substances 0.000 claims description 6
- 210000005260 human cell Anatomy 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 230000000890 antigenic effect Effects 0.000 claims description 4
- 230000021615 conjugation Effects 0.000 claims description 4
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 1
- 235000018102 proteins Nutrition 0.000 description 143
- 239000000499 gel Substances 0.000 description 88
- 229940088598 enzyme Drugs 0.000 description 56
- 238000006243 chemical reaction Methods 0.000 description 55
- 102000003886 Glycoproteins Human genes 0.000 description 41
- 108090000288 Glycoproteins Proteins 0.000 description 41
- 238000001514 detection method Methods 0.000 description 41
- 150000001540 azides Chemical class 0.000 description 40
- 150000001875 compounds Chemical class 0.000 description 39
- 239000012634 fragment Substances 0.000 description 30
- 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 29
- 239000000523 sample Substances 0.000 description 28
- 150000002772 monosaccharides Chemical group 0.000 description 24
- 239000000203 mixture Substances 0.000 description 22
- 239000000243 solution Substances 0.000 description 22
- 239000000370 acceptor Substances 0.000 description 21
- 239000000427 antigen Substances 0.000 description 21
- 108091007433 antigens Proteins 0.000 description 21
- 102000036639 antigens Human genes 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000000975 dye Substances 0.000 description 18
- 238000010186 staining Methods 0.000 description 18
- 235000001014 amino acid Nutrition 0.000 description 17
- 150000001413 amino acids Chemical class 0.000 description 17
- 108091006047 fluorescent proteins Proteins 0.000 description 17
- 102000034287 fluorescent proteins Human genes 0.000 description 17
- 102000004196 processed proteins & peptides Human genes 0.000 description 17
- 239000010979 ruby Substances 0.000 description 17
- 229910001750 ruby Inorganic materials 0.000 description 17
- 101001120790 Caenorhabditis elegans UDP-N-acetylglucosamine-peptide N-acetylglucosaminyltransferase Proteins 0.000 description 16
- 229940024606 amino acid Drugs 0.000 description 16
- 229960002685 biotin Drugs 0.000 description 15
- 235000020958 biotin Nutrition 0.000 description 15
- 239000011616 biotin Substances 0.000 description 15
- 239000003153 chemical reaction reagent Substances 0.000 description 15
- 229920000642 polymer Polymers 0.000 description 15
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 14
- 230000005284 excitation Effects 0.000 description 13
- 239000012528 membrane Substances 0.000 description 13
- 238000001466 metabolic labeling Methods 0.000 description 13
- 239000002773 nucleotide Substances 0.000 description 13
- 125000003729 nucleotide group Chemical group 0.000 description 13
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 13
- 235000010378 sodium ascorbate Nutrition 0.000 description 13
- 229960005055 sodium ascorbate Drugs 0.000 description 13
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 13
- 230000002255 enzymatic effect Effects 0.000 description 12
- 150000004676 glycans Chemical group 0.000 description 12
- 238000001727 in vivo Methods 0.000 description 12
- 108020004707 nucleic acids Proteins 0.000 description 12
- 150000007523 nucleic acids Chemical class 0.000 description 12
- 102000039446 nucleic acids Human genes 0.000 description 12
- 210000000628 antibody-producing cell Anatomy 0.000 description 11
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 11
- 239000003814 drug Substances 0.000 description 11
- 230000006870 function Effects 0.000 description 11
- 150000002632 lipids Chemical class 0.000 description 11
- 241000699666 Mus <mouse, genus> Species 0.000 description 10
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical class P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 10
- 239000011324 bead Substances 0.000 description 10
- 150000001720 carbohydrates Chemical class 0.000 description 10
- 125000003636 chemical group Chemical group 0.000 description 10
- 238000006352 cycloaddition reaction Methods 0.000 description 10
- 239000006166 lysate Substances 0.000 description 10
- 229940092253 ovalbumin Drugs 0.000 description 10
- 239000002245 particle Substances 0.000 description 10
- 241000283707 Capra Species 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 108060003951 Immunoglobulin Proteins 0.000 description 9
- 239000007993 MOPS buffer Substances 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 239000007983 Tris buffer Substances 0.000 description 9
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Substances ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 9
- 239000005556 hormone Substances 0.000 description 9
- 229940088597 hormone Drugs 0.000 description 9
- 102000018358 immunoglobulin Human genes 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 150000008163 sugars Chemical class 0.000 description 9
- ABZLKHKQJHEPAX-UHFFFAOYSA-N tetramethylrhodamine Chemical compound C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=CC=C1C([O-])=O ABZLKHKQJHEPAX-UHFFFAOYSA-N 0.000 description 9
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 9
- 108090001008 Avidin Proteins 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 108010058846 Ovalbumin Proteins 0.000 description 8
- 102000004316 Oxidoreductases Human genes 0.000 description 8
- 108090000854 Oxidoreductases Proteins 0.000 description 8
- 102000035195 Peptidases Human genes 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 108010007908 alpha-Crystallins Proteins 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 238000010790 dilution Methods 0.000 description 8
- 239000012895 dilution Substances 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 238000000338 in vitro Methods 0.000 description 8
- 239000003446 ligand Substances 0.000 description 8
- IYRGXJIJGHOCFS-UHFFFAOYSA-N neocuproine Chemical compound C1=C(C)N=C2C3=NC(C)=CC=C3C=CC2=C1 IYRGXJIJGHOCFS-UHFFFAOYSA-N 0.000 description 8
- 229920001282 polysaccharide Polymers 0.000 description 8
- 239000005017 polysaccharide Substances 0.000 description 8
- 239000011347 resin Substances 0.000 description 8
- 229920005989 resin Polymers 0.000 description 8
- 238000000926 separation method Methods 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 8
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 8
- 108020004414 DNA Proteins 0.000 description 7
- 102000007362 alpha-Crystallins Human genes 0.000 description 7
- 230000008859 change Effects 0.000 description 7
- 229920001184 polypeptide Polymers 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 230000035945 sensitivity Effects 0.000 description 7
- 230000009870 specific binding Effects 0.000 description 7
- 238000012546 transfer Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 241000287828 Gallus gallus Species 0.000 description 6
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 6
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 6
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 6
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 6
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 6
- 108010062374 Myoglobin Proteins 0.000 description 6
- 102100030856 Myoglobin Human genes 0.000 description 6
- CVRXLMUYFMERMJ-UHFFFAOYSA-N N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine Chemical compound C=1C=CC=NC=1CN(CC=1N=CC=CC=1)CCN(CC=1N=CC=CC=1)CC1=CC=CC=N1 CVRXLMUYFMERMJ-UHFFFAOYSA-N 0.000 description 6
- 108091034117 Oligonucleotide Proteins 0.000 description 6
- 229910019142 PO4 Inorganic materials 0.000 description 6
- 102000003992 Peroxidases Human genes 0.000 description 6
- 238000003800 Staudinger reaction Methods 0.000 description 6
- 108010090804 Streptavidin Proteins 0.000 description 6
- 235000010724 Wisteria floribunda Nutrition 0.000 description 6
- PBLNJFVQMUMOJY-JXZOILRNSA-N [(z)-[(3r,4r,5s,6r)-3-acetamido-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-ylidene]amino] n-phenylcarbamate Chemical compound CC(=O)N[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O\C1=N/OC(=O)NC1=CC=CC=C1 PBLNJFVQMUMOJY-JXZOILRNSA-N 0.000 description 6
- 239000010949 copper Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 235000021317 phosphate Nutrition 0.000 description 6
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 5
- 102000004127 Cytokines Human genes 0.000 description 5
- 108090000695 Cytokines Proteins 0.000 description 5
- 239000002033 PVDF binder Substances 0.000 description 5
- 102000057297 Pepsin A Human genes 0.000 description 5
- 108090000284 Pepsin A Proteins 0.000 description 5
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 239000004202 carbamide Substances 0.000 description 5
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 5
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 5
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 5
- 229930182830 galactose Natural products 0.000 description 5
- 239000003102 growth factor Substances 0.000 description 5
- 150000002500 ions Chemical class 0.000 description 5
- QDLAGTHXVHQKRE-UHFFFAOYSA-N lichenxanthone Natural products COC1=CC(O)=C2C(=O)C3=C(C)C=C(OC)C=C3OC2=C1 QDLAGTHXVHQKRE-UHFFFAOYSA-N 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 230000002503 metabolic effect Effects 0.000 description 5
- 239000002777 nucleoside Substances 0.000 description 5
- 229940111202 pepsin Drugs 0.000 description 5
- 108040007629 peroxidase activity proteins Proteins 0.000 description 5
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 5
- 108060006184 phycobiliprotein Proteins 0.000 description 5
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 5
- 230000003595 spectral effect Effects 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 239000003053 toxin Substances 0.000 description 5
- 231100000765 toxin Toxicity 0.000 description 5
- 108700012359 toxins Proteins 0.000 description 5
- 238000001262 western blot Methods 0.000 description 5
- QGKMIGUHVLGJBR-UHFFFAOYSA-M (4z)-1-(3-methylbutyl)-4-[[1-(3-methylbutyl)quinolin-1-ium-4-yl]methylidene]quinoline;iodide Chemical compound [I-].C12=CC=CC=C2N(CCC(C)C)C=CC1=CC1=CC=[N+](CCC(C)C)C2=CC=CC=C12 QGKMIGUHVLGJBR-UHFFFAOYSA-M 0.000 description 4
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 4
- 229920000936 Agarose Polymers 0.000 description 4
- 229920002307 Dextran Polymers 0.000 description 4
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
- 238000006736 Huisgen cycloaddition reaction Methods 0.000 description 4
- 108090001090 Lectins Proteins 0.000 description 4
- 102000004856 Lectins Human genes 0.000 description 4
- 239000007987 MES buffer Substances 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 108090000526 Papain Proteins 0.000 description 4
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 4
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 4
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 4
- 125000000304 alkynyl group Chemical group 0.000 description 4
- 125000000539 amino acid group Chemical group 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000013592 cell lysate Substances 0.000 description 4
- 239000003638 chemical reducing agent Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000012650 click reaction Methods 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 230000013595 glycosylation Effects 0.000 description 4
- 238000006206 glycosylation reaction Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- QRMZSPFSDQBLIX-UHFFFAOYSA-N homovanillic acid Chemical compound COC1=CC(CC(O)=O)=CC=C1O QRMZSPFSDQBLIX-UHFFFAOYSA-N 0.000 description 4
- 210000004408 hybridoma Anatomy 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 238000003384 imaging method Methods 0.000 description 4
- 230000002163 immunogen Effects 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 239000002523 lectin Substances 0.000 description 4
- 238000002493 microarray Methods 0.000 description 4
- 239000011859 microparticle Substances 0.000 description 4
- 239000003068 molecular probe Substances 0.000 description 4
- 150000003833 nucleoside derivatives Chemical class 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- 229910052698 phosphorus Inorganic materials 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- ZCCUUQDIBDJBTK-UHFFFAOYSA-N psoralen Chemical compound C1=C2OC(=O)C=CC2=CC2=C1OC=C2 ZCCUUQDIBDJBTK-UHFFFAOYSA-N 0.000 description 4
- BBEAQIROQSPTKN-UHFFFAOYSA-N pyrene Chemical compound C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 BBEAQIROQSPTKN-UHFFFAOYSA-N 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 238000000539 two dimensional gel electrophoresis Methods 0.000 description 4
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 3
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 108010088751 Albumins Proteins 0.000 description 3
- 102000009027 Albumins Human genes 0.000 description 3
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 3
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 3
- 101100067708 Caenorhabditis elegans galt-1 gene Proteins 0.000 description 3
- 101710112752 Cytotoxin Proteins 0.000 description 3
- 108010092160 Dactinomycin Proteins 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 229920001917 Ficoll Polymers 0.000 description 3
- 102000004157 Hydrolases Human genes 0.000 description 3
- 108090000604 Hydrolases Proteins 0.000 description 3
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical class C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 3
- 102000000588 Interleukin-2 Human genes 0.000 description 3
- 108010002350 Interleukin-2 Proteins 0.000 description 3
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 3
- 108090001030 Lipoproteins Proteins 0.000 description 3
- 102000004895 Lipoproteins Human genes 0.000 description 3
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 108010089430 Phosphoproteins Proteins 0.000 description 3
- 102000007982 Phosphoproteins Human genes 0.000 description 3
- 239000004793 Polystyrene Substances 0.000 description 3
- 102100030122 Protein O-GlcNAcase Human genes 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 3
- 101710120037 Toxin CcdB Proteins 0.000 description 3
- 102000004357 Transferases Human genes 0.000 description 3
- 108090000992 Transferases Proteins 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 238000010958 [3+2] cycloaddition reaction Methods 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 238000000862 absorption spectrum Methods 0.000 description 3
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 3
- 108010004469 allophycocyanin Proteins 0.000 description 3
- 239000012491 analyte Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N benzo-alpha-pyrone Natural products C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- 231100000599 cytotoxic agent Toxicity 0.000 description 3
- 239000002619 cytotoxin Substances 0.000 description 3
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000001962 electrophoresis Methods 0.000 description 3
- 238000000295 emission spectrum Methods 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 229910052737 gold Inorganic materials 0.000 description 3
- 239000010931 gold Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 230000005291 magnetic effect Effects 0.000 description 3
- 150000002739 metals Chemical class 0.000 description 3
- 229950006780 n-acetylglucosamine Drugs 0.000 description 3
- 210000003463 organelle Anatomy 0.000 description 3
- 229940055729 papain Drugs 0.000 description 3
- 235000019834 papain Nutrition 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 230000000704 physical effect Effects 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 229920003023 plastic Polymers 0.000 description 3
- 229920002401 polyacrylamide Polymers 0.000 description 3
- 229920002223 polystyrene Polymers 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 235000019833 protease Nutrition 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 3
- 239000012146 running buffer Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 229920001059 synthetic polymer Polymers 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- 150000003732 xanthenes Chemical class 0.000 description 3
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 2
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
- UFBJCMHMOXMLKC-UHFFFAOYSA-N 2,4-dinitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O UFBJCMHMOXMLKC-UHFFFAOYSA-N 0.000 description 2
- KUWPCJHYPSUOFW-YBXAARCKSA-N 2-nitrophenyl beta-D-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CC=CC=C1[N+]([O-])=O KUWPCJHYPSUOFW-YBXAARCKSA-N 0.000 description 2
- ZTOBILYWTYHOJB-WBCGDKOGSA-N 3',6'-bis[[(2s,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy]spiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CC=C2C3(C4=CC=CC=C4C(=O)O3)C3=CC=C(O[C@H]4[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O4)O)C=C3OC2=C1 ZTOBILYWTYHOJB-WBCGDKOGSA-N 0.000 description 2
- HSTOKWSFWGCZMH-UHFFFAOYSA-N 3,3'-diaminobenzidine Chemical compound C1=C(N)C(N)=CC=C1C1=CC=C(N)C(N)=C1 HSTOKWSFWGCZMH-UHFFFAOYSA-N 0.000 description 2
- VXGRJERITKFWPL-UHFFFAOYSA-N 4',5'-Dihydropsoralen Natural products C1=C2OC(=O)C=CC2=CC2=C1OCC2 VXGRJERITKFWPL-UHFFFAOYSA-N 0.000 description 2
- OPIFSICVWOWJMJ-AEOCFKNESA-N 5-bromo-4-chloro-3-indolyl beta-D-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CNC2=CC=C(Br)C(Cl)=C12 OPIFSICVWOWJMJ-AEOCFKNESA-N 0.000 description 2
- OXEUETBFKVCRNP-UHFFFAOYSA-N 9-ethyl-3-carbazolamine Chemical compound NC1=CC=C2N(CC)C3=CC=CC=C3C2=C1 OXEUETBFKVCRNP-UHFFFAOYSA-N 0.000 description 2
- 102000015693 Actin Depolymerizing Factors Human genes 0.000 description 2
- 108010038798 Actin Depolymerizing Factors Proteins 0.000 description 2
- 229920000945 Amylopectin Polymers 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 2
- 108090000322 Cholinesterases Proteins 0.000 description 2
- 102000003914 Cholinesterases Human genes 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 238000000018 DNA microarray Methods 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 239000004366 Glucose oxidase Substances 0.000 description 2
- 108010015776 Glucose oxidase Proteins 0.000 description 2
- 108010060309 Glucuronidase Proteins 0.000 description 2
- 102000053187 Glucuronidase Human genes 0.000 description 2
- 229920002527 Glycogen Polymers 0.000 description 2
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 2
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 102000006947 Histones Human genes 0.000 description 2
- 108010033040 Histones Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
- 102000018071 Immunoglobulin Fc Fragments Human genes 0.000 description 2
- 108010091135 Immunoglobulin Fc Fragments Proteins 0.000 description 2
- 102000006992 Interferon-alpha Human genes 0.000 description 2
- 108010047761 Interferon-alpha Proteins 0.000 description 2
- 102000000589 Interleukin-1 Human genes 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 229920001202 Inulin Polymers 0.000 description 2
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 2
- 108090001060 Lipase Proteins 0.000 description 2
- 102000004882 Lipase Human genes 0.000 description 2
- 239000004367 Lipase Substances 0.000 description 2
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- 102000008072 Lymphokines Human genes 0.000 description 2
- 108010074338 Lymphokines Proteins 0.000 description 2
- 229920000057 Mannan Polymers 0.000 description 2
- 108010090054 Membrane Glycoproteins Proteins 0.000 description 2
- 102000012750 Membrane Glycoproteins Human genes 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 102000015728 Mucins Human genes 0.000 description 2
- 108010063954 Mucins Proteins 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 2
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 2
- 102100038358 Prostate-specific antigen Human genes 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- VGQOVCHZGQWAOI-UHFFFAOYSA-N UNPD55612 Natural products N1C(O)C2CC(C=CC(N)=O)=CN2C(=O)C2=CC=C(C)C(O)=C12 VGQOVCHZGQWAOI-UHFFFAOYSA-N 0.000 description 2
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 2
- 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 2
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 229960000548 alemtuzumab Drugs 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
- VGQOVCHZGQWAOI-HYUHUPJXSA-N anthramycin Chemical compound N1[C@@H](O)[C@@H]2CC(\C=C\C(N)=O)=CN2C(=O)C2=CC=C(C)C(O)=C12 VGQOVCHZGQWAOI-HYUHUPJXSA-N 0.000 description 2
- 238000000149 argon plasma sintering Methods 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 description 2
- 238000000429 assembly Methods 0.000 description 2
- 230000000712 assembly Effects 0.000 description 2
- CUFNKYGDVFVPHO-UHFFFAOYSA-N azulene Chemical compound C1=CC=CC2=CC=CC2=C1 CUFNKYGDVFVPHO-UHFFFAOYSA-N 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 2
- 229960000397 bevacizumab Drugs 0.000 description 2
- 230000008512 biological response Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 description 2
- 229960005395 cetuximab Drugs 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 229940048961 cholinesterase Drugs 0.000 description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
- 239000000356 contaminant Substances 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 235000001671 coumarin Nutrition 0.000 description 2
- 150000004775 coumarins Chemical class 0.000 description 2
- 150000001907 coumarones Chemical class 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 229960000640 dactinomycin Drugs 0.000 description 2
- 229960000975 daunorubicin Drugs 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- 238000000695 excitation spectrum Methods 0.000 description 2
- 239000010408 film Substances 0.000 description 2
- GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthrene Natural products C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 description 2
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 2
- 238000001502 gel electrophoresis Methods 0.000 description 2
- 229960000578 gemtuzumab Drugs 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 229940116332 glucose oxidase Drugs 0.000 description 2
- 235000019420 glucose oxidase Nutrition 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 229940096919 glycogen Drugs 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 239000005090 green fluorescent protein Substances 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 125000001072 heteroaryl group Chemical group 0.000 description 2
- 108010045982 hexosaminidase C Proteins 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- JYJIGFIDKWBXDU-MNNPPOADSA-N inulin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@]1(OC[C@]2(OC[C@]3(OC[C@]4(OC[C@]5(OC[C@]6(OC[C@]7(OC[C@]8(OC[C@]9(OC[C@]%10(OC[C@]%11(OC[C@]%12(OC[C@]%13(OC[C@]%14(OC[C@]%15(OC[C@]%16(OC[C@]%17(OC[C@]%18(OC[C@]%19(OC[C@]%20(OC[C@]%21(OC[C@]%22(OC[C@]%23(OC[C@]%24(OC[C@]%25(OC[C@]%26(OC[C@]%27(OC[C@]%28(OC[C@]%29(OC[C@]%30(OC[C@]%31(OC[C@]%32(OC[C@]%33(OC[C@]%34(OC[C@]%35(OC[C@]%36(O[C@@H]%37[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O%37)O)[C@H]([C@H](O)[C@@H](CO)O%36)O)[C@H]([C@H](O)[C@@H](CO)O%35)O)[C@H]([C@H](O)[C@@H](CO)O%34)O)[C@H]([C@H](O)[C@@H](CO)O%33)O)[C@H]([C@H](O)[C@@H](CO)O%32)O)[C@H]([C@H](O)[C@@H](CO)O%31)O)[C@H]([C@H](O)[C@@H](CO)O%30)O)[C@H]([C@H](O)[C@@H](CO)O%29)O)[C@H]([C@H](O)[C@@H](CO)O%28)O)[C@H]([C@H](O)[C@@H](CO)O%27)O)[C@H]([C@H](O)[C@@H](CO)O%26)O)[C@H]([C@H](O)[C@@H](CO)O%25)O)[C@H]([C@H](O)[C@@H](CO)O%24)O)[C@H]([C@H](O)[C@@H](CO)O%23)O)[C@H]([C@H](O)[C@@H](CO)O%22)O)[C@H]([C@H](O)[C@@H](CO)O%21)O)[C@H]([C@H](O)[C@@H](CO)O%20)O)[C@H]([C@H](O)[C@@H](CO)O%19)O)[C@H]([C@H](O)[C@@H](CO)O%18)O)[C@H]([C@H](O)[C@@H](CO)O%17)O)[C@H]([C@H](O)[C@@H](CO)O%16)O)[C@H]([C@H](O)[C@@H](CO)O%15)O)[C@H]([C@H](O)[C@@H](CO)O%14)O)[C@H]([C@H](O)[C@@H](CO)O%13)O)[C@H]([C@H](O)[C@@H](CO)O%12)O)[C@H]([C@H](O)[C@@H](CO)O%11)O)[C@H]([C@H](O)[C@@H](CO)O%10)O)[C@H]([C@H](O)[C@@H](CO)O9)O)[C@H]([C@H](O)[C@@H](CO)O8)O)[C@H]([C@H](O)[C@@H](CO)O7)O)[C@H]([C@H](O)[C@@H](CO)O6)O)[C@H]([C@H](O)[C@@H](CO)O5)O)[C@H]([C@H](O)[C@@H](CO)O4)O)[C@H]([C@H](O)[C@@H](CO)O3)O)[C@H]([C@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 JYJIGFIDKWBXDU-MNNPPOADSA-N 0.000 description 2
- 229940029339 inulin Drugs 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 235000019421 lipase Nutrition 0.000 description 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 2
- 229910052753 mercury Inorganic materials 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- FNEZBBILNYNQGC-UHFFFAOYSA-N methyl 2-(3,6-diamino-9h-xanthen-9-yl)benzoate Chemical compound COC(=O)C1=CC=CC=C1C1C2=CC=C(N)C=C2OC2=CC(N)=CC=C21 FNEZBBILNYNQGC-UHFFFAOYSA-N 0.000 description 2
- 239000004005 microsphere Substances 0.000 description 2
- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- 102000035118 modified proteins Human genes 0.000 description 2
- 108091005573 modified proteins Proteins 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 150000004893 oxazines Chemical class 0.000 description 2
- MPQXHAGKBWFSNV-UHFFFAOYSA-N oxidophosphanium Chemical class [PH3]=O MPQXHAGKBWFSNV-UHFFFAOYSA-N 0.000 description 2
- 229960001972 panitumumab Drugs 0.000 description 2
- 244000045947 parasite Species 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 150000003003 phosphines Chemical class 0.000 description 2
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical class OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 229960003171 plicamycin Drugs 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 102000035123 post-translationally modified proteins Human genes 0.000 description 2
- 108091005626 post-translationally modified proteins Proteins 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- 235000019419 proteases Nutrition 0.000 description 2
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 2
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 238000010188 recombinant method Methods 0.000 description 2
- HSSLDCABUXLXKM-UHFFFAOYSA-N resorufin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3N=C21 HSSLDCABUXLXKM-UHFFFAOYSA-N 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 229960004641 rituximab Drugs 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 239000010409 thin film Substances 0.000 description 2
- WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- 229960000575 trastuzumab Drugs 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- DZGWFCGJZKJUFP-UHFFFAOYSA-N tyramine Chemical compound NCCC1=CC=C(O)C=C1 DZGWFCGJZKJUFP-UHFFFAOYSA-N 0.000 description 2
- 229960003048 vinblastine Drugs 0.000 description 2
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 2
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
- 229960004528 vincristine Drugs 0.000 description 2
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 2
- IMZBXSAKACGTPH-UHFFFAOYSA-N (3-oxo-6'-phosphonooxyspiro[2-benzofuran-1,9'-xanthene]-3'-yl) dihydrogen phosphate Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(OP(O)(O)=O)C=C1OC1=CC(OP(O)(=O)O)=CC=C21 IMZBXSAKACGTPH-UHFFFAOYSA-N 0.000 description 1
- BCHIXGBGRHLSBE-UHFFFAOYSA-N (4-methyl-2-oxochromen-7-yl) dihydrogen phosphate Chemical compound C1=C(OP(O)(O)=O)C=CC2=C1OC(=O)C=C2C BCHIXGBGRHLSBE-UHFFFAOYSA-N 0.000 description 1
- AUTOLBMXDDTRRT-JGVFFNPUSA-N (4R,5S)-dethiobiotin Chemical compound C[C@@H]1NC(=O)N[C@@H]1CCCCCC(O)=O AUTOLBMXDDTRRT-JGVFFNPUSA-N 0.000 description 1
- CJNPEPJBIHGEMU-UHFFFAOYSA-N (5-bromo-6-chloro-1h-indol-3-yl) dihydrogen phosphate Chemical compound ClC1=C(Br)C=C2C(OP(O)(=O)O)=CNC2=C1 CJNPEPJBIHGEMU-UHFFFAOYSA-N 0.000 description 1
- RCKGZPVKDHAHFN-UHFFFAOYSA-N (6,8-difluoro-7-hydroxy-4-methyl-2-oxochromen-3-yl) dihydrogen phosphate Chemical compound FC1=C(O)C(F)=CC2=C1OC(=O)C(OP(O)(O)=O)=C2C RCKGZPVKDHAHFN-UHFFFAOYSA-N 0.000 description 1
- IFQGEGPISKJALV-UHFFFAOYSA-N (6-chloro-1h-indol-3-yl) dihydrogen phosphate Chemical compound ClC1=CC=C2C(OP(O)(=O)O)=CNC2=C1 IFQGEGPISKJALV-UHFFFAOYSA-N 0.000 description 1
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- PKYCWFICOKSIHZ-UHFFFAOYSA-N 1-(3,7-dihydroxyphenoxazin-10-yl)ethanone Chemical compound OC1=CC=C2N(C(=O)C)C3=CC=C(O)C=C3OC2=C1 PKYCWFICOKSIHZ-UHFFFAOYSA-N 0.000 description 1
- GZCWLCBFPRFLKL-UHFFFAOYSA-N 1-prop-2-ynoxypropan-2-ol Chemical compound CC(O)COCC#C GZCWLCBFPRFLKL-UHFFFAOYSA-N 0.000 description 1
- TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
- HIYWOHBEPVGIQN-UHFFFAOYSA-N 1h-benzo[g]indole Chemical compound C1=CC=CC2=C(NC=C3)C3=CC=C21 HIYWOHBEPVGIQN-UHFFFAOYSA-N 0.000 description 1
- QGVQERKFDGXVOE-UHFFFAOYSA-N 1h-imidazol-2-ylphosphane Chemical compound PC1=NC=CN1 QGVQERKFDGXVOE-UHFFFAOYSA-N 0.000 description 1
- AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 description 1
- CHUGKEQJSLOLHL-UHFFFAOYSA-N 2,2-Bis(bromomethyl)propane-1,3-diol Chemical compound OCC(CO)(CBr)CBr CHUGKEQJSLOLHL-UHFFFAOYSA-N 0.000 description 1
- YHIABRIDBIGEOW-UHFFFAOYSA-N 2,9-dihydro-1h-xanthene Chemical compound C1=CC=C2CC(CCC=C3)=C3OC2=C1 YHIABRIDBIGEOW-UHFFFAOYSA-N 0.000 description 1
- PIINGYXNCHTJTF-UHFFFAOYSA-N 2-(2-azaniumylethylamino)acetate Chemical compound NCCNCC(O)=O PIINGYXNCHTJTF-UHFFFAOYSA-N 0.000 description 1
- IXZONVAEGFOVSF-UHFFFAOYSA-N 2-(5'-chloro-2'-phosphoryloxyphenyl)-6-chloro-4-(3H)-quinazolinone Chemical compound OP(O)(=O)OC1=CC=C(Cl)C=C1C1=NC(=O)C2=CC(Cl)=CC=C2N1 IXZONVAEGFOVSF-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- UJVBZCCNLAAMOV-UHFFFAOYSA-N 2h-1,2-benzothiazine Chemical compound C1=CC=C2C=CNSC2=C1 UJVBZCCNLAAMOV-UHFFFAOYSA-N 0.000 description 1
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 description 1
- WCICUBWFIOLNSV-UHFFFAOYSA-N 2h-oxazine-3,4-diamine Chemical class NC1=C(N)C=CON1 WCICUBWFIOLNSV-UHFFFAOYSA-N 0.000 description 1
- OALHHIHQOFIMEF-UHFFFAOYSA-N 3',6'-dihydroxy-2',4',5',7'-tetraiodo-3h-spiro[2-benzofuran-1,9'-xanthene]-3-one Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(I)C(O)=C(I)C=C21 OALHHIHQOFIMEF-UHFFFAOYSA-N 0.000 description 1
- KDXNYSZNOWTPLE-UHFFFAOYSA-N 3'-hydroxy-6'-methoxyspiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(OC)=CC=C21 KDXNYSZNOWTPLE-UHFFFAOYSA-N 0.000 description 1
- 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 1
- JRBJSXQPQWSCCF-UHFFFAOYSA-N 3,3'-Dimethoxybenzidine Chemical compound C1=C(N)C(OC)=CC(C=2C=C(OC)C(N)=CC=2)=C1 JRBJSXQPQWSCCF-UHFFFAOYSA-N 0.000 description 1
- IELMMGIVWJNLEX-UHFFFAOYSA-N 3,3-difluorocyclooctyne Chemical compound FC1(F)CCCCCC#C1 IELMMGIVWJNLEX-UHFFFAOYSA-N 0.000 description 1
- GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical compound C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 description 1
- WKALLSVICJPZTM-UHFFFAOYSA-N 3-[decyl(dimethyl)azaniumyl]propane-1-sulfonate Chemical compound CCCCCCCCCC[N+](C)(C)CCCS([O-])(=O)=O WKALLSVICJPZTM-UHFFFAOYSA-N 0.000 description 1
- WHNPOQXWAMXPTA-UHFFFAOYSA-N 3-methylbut-2-enamide Chemical compound CC(C)=CC(N)=O WHNPOQXWAMXPTA-UHFFFAOYSA-N 0.000 description 1
- XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 1
- YRNWIFYIFSBPAU-UHFFFAOYSA-N 4-[4-(dimethylamino)phenyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1C1=CC=C(N(C)C)C=C1 YRNWIFYIFSBPAU-UHFFFAOYSA-N 0.000 description 1
- BHOXPDZNQUGRRH-UHFFFAOYSA-N 4-amino-4h-oxazin-3-one Chemical class NC1C=CONC1=O BHOXPDZNQUGRRH-UHFFFAOYSA-N 0.000 description 1
- LVSPDZAGCBEQAV-UHFFFAOYSA-N 4-chloronaphthalen-1-ol Chemical compound C1=CC=C2C(O)=CC=C(Cl)C2=C1 LVSPDZAGCBEQAV-UHFFFAOYSA-N 0.000 description 1
- SXTSBZBQQRIYCU-UHFFFAOYSA-N 4-guanidinobenzoic acid Chemical compound NC(=N)NC1=CC=C(C(O)=O)C=C1 SXTSBZBQQRIYCU-UHFFFAOYSA-N 0.000 description 1
- YUDPTGPSBJVHCN-DZQJYWQESA-N 4-methylumbelliferyl beta-D-galactoside Chemical compound C1=CC=2C(C)=CC(=O)OC=2C=C1O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O YUDPTGPSBJVHCN-DZQJYWQESA-N 0.000 description 1
- IFBHRQDFSNCLOZ-YBXAARCKSA-N 4-nitrophenyl-beta-D-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CC=C([N+]([O-])=O)C=C1 IFBHRQDFSNCLOZ-YBXAARCKSA-N 0.000 description 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
- JJXUHRONZVELPY-NHCYSSNCSA-N 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-n-prop-2-ynylpentanamide Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)NCC#C)SC[C@@H]21 JJXUHRONZVELPY-NHCYSSNCSA-N 0.000 description 1
- DZANYXOTJVLAEE-UHFFFAOYSA-N 6,8-difluoro-4-methylumbelliferyl phosphate Chemical compound FC1=C(OP(O)(O)=O)C(F)=CC2=C1OC(=O)C=C2C DZANYXOTJVLAEE-UHFFFAOYSA-N 0.000 description 1
- JVKVVXNSKFDAIB-UHFFFAOYSA-N 6-aminoxanthen-3-one Chemical class C1=CC(=O)C=C2OC3=CC(N)=CC=C3C=C21 JVKVVXNSKFDAIB-UHFFFAOYSA-N 0.000 description 1
- HXYAESYPQJYEBJ-UHFFFAOYSA-N 6-hydroxyxanthen-3-one Chemical class C1=CC(=O)C=C2OC3=CC(O)=CC=C3C=C21 HXYAESYPQJYEBJ-UHFFFAOYSA-N 0.000 description 1
- DJXIADRXORLNJX-UHFFFAOYSA-N 6-iminoxanthen-3-amine Chemical class C1=CC(=N)C=C2OC3=CC(N)=CC=C3C=C21 DJXIADRXORLNJX-UHFFFAOYSA-N 0.000 description 1
- QULZFZMEBOATFS-DISONHOPSA-N 7-[(2s,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenoxazin-3-one Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CC=C(N=C2C(=CC(=O)C=C2)O2)C2=C1 QULZFZMEBOATFS-DISONHOPSA-N 0.000 description 1
- 108010066676 Abrin Proteins 0.000 description 1
- 108010051457 Acid Phosphatase Proteins 0.000 description 1
- 102000013563 Acid Phosphatase Human genes 0.000 description 1
- 108010000239 Aequorin Proteins 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 239000012099 Alexa Fluor family Substances 0.000 description 1
- 108091029845 Aminoallyl nucleotide Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 101710180684 Beta-hexosaminidase Proteins 0.000 description 1
- 101710124976 Beta-hexosaminidase A Proteins 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 1
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 108010004032 Bromelains Proteins 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 101100314454 Caenorhabditis elegans tra-1 gene Proteins 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 108010035722 Chloride peroxidase Proteins 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 108091000069 Cystinyl Aminopeptidase Proteins 0.000 description 1
- 102000030900 Cystinyl aminopeptidase Human genes 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- 102000000634 Cytochrome c oxidase subunit IV Human genes 0.000 description 1
- 108050008072 Cytochrome c oxidase subunit IV Proteins 0.000 description 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- BRDJPCFGLMKJRU-UHFFFAOYSA-N DDAO Chemical compound ClC1=C(O)C(Cl)=C2C(C)(C)C3=CC(=O)C=CC3=NC2=C1 BRDJPCFGLMKJRU-UHFFFAOYSA-N 0.000 description 1
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 238000005698 Diels-Alder reaction Methods 0.000 description 1
- SHIBSTMRCDJXLN-UHFFFAOYSA-N Digoxigenin Natural products C1CC(C2C(C3(C)CCC(O)CC3CC2)CC2O)(O)C2(C)C1C1=CC(=O)OC1 SHIBSTMRCDJXLN-UHFFFAOYSA-N 0.000 description 1
- BVTJGGGYKAMDBN-UHFFFAOYSA-N Dioxetane Chemical class C1COO1 BVTJGGGYKAMDBN-UHFFFAOYSA-N 0.000 description 1
- 102000016607 Diphtheria Toxin Human genes 0.000 description 1
- 108010053187 Diphtheria Toxin Proteins 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 102000004533 Endonucleases Human genes 0.000 description 1
- 102100029727 Enteropeptidase Human genes 0.000 description 1
- 108010013369 Enteropeptidase Proteins 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 108060002716 Exonuclease Proteins 0.000 description 1
- UYZYJXHZHAOLLC-UHFFFAOYSA-N F.C1=CC=C2CC3=CC=CC=C3OC2=C1 Chemical compound F.C1=CC=C2CC3=CC=CC=C3OC2=C1 UYZYJXHZHAOLLC-UHFFFAOYSA-N 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 1
- 101150102398 Galt gene Proteins 0.000 description 1
- 101710107035 Gamma-glutamyltranspeptidase Proteins 0.000 description 1
- 102100022624 Glucoamylase Human genes 0.000 description 1
- 108050008938 Glucoamylases Proteins 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 101710173228 Glutathione hydrolase proenzyme Proteins 0.000 description 1
- 229930186217 Glycolipid Natural products 0.000 description 1
- 108700023372 Glycosyltransferases Proteins 0.000 description 1
- 102000051366 Glycosyltransferases Human genes 0.000 description 1
- 108010026389 Gramicidin Proteins 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 102000003964 Histone deacetylase Human genes 0.000 description 1
- 108090000353 Histone deacetylase Proteins 0.000 description 1
- 102000003864 Human Follicle Stimulating Hormone Human genes 0.000 description 1
- 108010082302 Human Follicle Stimulating Hormone 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
- 108010003272 Hyaluronate lyase Proteins 0.000 description 1
- 102000009066 Hyaluronoglucosaminidase Human genes 0.000 description 1
- 102000028555 IgG binding proteins Human genes 0.000 description 1
- 108091009325 IgG binding proteins Proteins 0.000 description 1
- 102000005755 Intercellular Signaling Peptides and Proteins Human genes 0.000 description 1
- 108010070716 Intercellular Signaling Peptides and Proteins Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 102000004195 Isomerases Human genes 0.000 description 1
- 108090000769 Isomerases Proteins 0.000 description 1
- 108060005987 Kallikrein Proteins 0.000 description 1
- 102000001399 Kallikrein Human genes 0.000 description 1
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 102000009151 Luteinizing Hormone Human genes 0.000 description 1
- 108010073521 Luteinizing Hormone Proteins 0.000 description 1
- 102000004317 Lyases Human genes 0.000 description 1
- 108090000856 Lyases Proteins 0.000 description 1
- 102000004083 Lymphotoxin-alpha Human genes 0.000 description 1
- 108090000542 Lymphotoxin-alpha Proteins 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- VFKZTMPDYBFSTM-KVTDHHQDSA-N Mitobronitol Chemical compound BrC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CBr VFKZTMPDYBFSTM-KVTDHHQDSA-N 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- BKAYIFDRRZZKNF-VIFPVBQESA-N N-acetylcarnosine Chemical compound CC(=O)NCCC(=O)N[C@H](C(O)=O)CC1=CN=CN1 BKAYIFDRRZZKNF-VIFPVBQESA-N 0.000 description 1
- IXQIUDNVFVTQLJ-UHFFFAOYSA-N Naphthofluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C(C=CC=1C3=CC=C(O)C=1)=C3OC1=C2C=CC2=CC(O)=CC=C21 IXQIUDNVFVTQLJ-UHFFFAOYSA-N 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 102000015336 Nerve Growth Factor Human genes 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108010047320 Pepsinogen A Proteins 0.000 description 1
- 108091093037 Peptide nucleic acid Proteins 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 1
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 101710081801 Protein O-GlcNAcase Proteins 0.000 description 1
- 108010026552 Proteome Proteins 0.000 description 1
- 101000762949 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) Exotoxin A Proteins 0.000 description 1
- 101710199095 Putative beta-hexosaminidase Proteins 0.000 description 1
- 108091007187 Reductases Proteins 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 235000004443 Ricinus communis Nutrition 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 102100038803 Somatotropin Human genes 0.000 description 1
- PJANXHGTPQOBST-VAWYXSNFSA-N Stilbene Natural products C=1C=CC=CC=1/C=C/C1=CC=CC=C1 PJANXHGTPQOBST-VAWYXSNFSA-N 0.000 description 1
- 244000028419 Styrax benzoin Species 0.000 description 1
- 235000000126 Styrax benzoin Nutrition 0.000 description 1
- 108010091105 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 1
- 102000018075 Subfamily B ATP Binding Cassette Transporter Human genes 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 102000005262 Sulfatase Human genes 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 235000008411 Sumatra benzointree Nutrition 0.000 description 1
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
- 108010092262 T-Cell Antigen Receptors Proteins 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 102000011923 Thyrotropin Human genes 0.000 description 1
- 108010061174 Thyrotropin Proteins 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- HSCJRCZFDFQWRP-ABVWGUQPSA-N UDP-alpha-D-galactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1OP(O)(=O)OP(O)(=O)OC[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C(NC(=O)C=C2)=O)O1 HSCJRCZFDFQWRP-ABVWGUQPSA-N 0.000 description 1
- GBOGMAARMMDZGR-UHFFFAOYSA-N UNPD149280 Natural products N1C(=O)C23OC(=O)C=CC(O)CCCC(C)CC=CC3C(O)C(=C)C(C)C2C1CC1=CC=CC=C1 GBOGMAARMMDZGR-UHFFFAOYSA-N 0.000 description 1
- HSCJRCZFDFQWRP-UHFFFAOYSA-N Uridindiphosphoglukose Natural products OC1C(O)C(O)C(CO)OC1OP(O)(=O)OP(O)(=O)OCC1C(O)C(O)C(N2C(NC(=O)C=C2)=O)O1 HSCJRCZFDFQWRP-UHFFFAOYSA-N 0.000 description 1
- 108070000030 Viral receptors Proteins 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229930183665 actinomycin Natural products 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 239000004964 aerogel Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 239000013566 allergen Substances 0.000 description 1
- 108010081373 alpha-galactosidase I Proteins 0.000 description 1
- 108010014595 alpha-galactosidase II Proteins 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 239000003080 antimitotic agent Substances 0.000 description 1
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 229940121357 antivirals Drugs 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 108010030694 avidin-horseradish peroxidase complex Proteins 0.000 description 1
- OHDRQQURAXLVGJ-HLVWOLMTSA-N azane;(2e)-3-ethyl-2-[(e)-(3-ethyl-6-sulfo-1,3-benzothiazol-2-ylidene)hydrazinylidene]-1,3-benzothiazole-6-sulfonic acid Chemical compound [NH4+].[NH4+].S/1C2=CC(S([O-])(=O)=O)=CC=C2N(CC)C\1=N/N=C1/SC2=CC(S([O-])(=O)=O)=CC=C2N1CC OHDRQQURAXLVGJ-HLVWOLMTSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- SJCPQBRQOOJBFM-UHFFFAOYSA-N benzo[a]phenalen-1-one Chemical compound C1=CC=C2C(C(=O)C=C3)=C4C3=CC=CC4=CC2=C1 SJCPQBRQOOJBFM-UHFFFAOYSA-N 0.000 description 1
- 229960002130 benzoin Drugs 0.000 description 1
- 150000005130 benzoxazines Chemical class 0.000 description 1
- 108010019077 beta-Amylase Proteins 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 108010051210 beta-Fructofuranosidase Proteins 0.000 description 1
- 102000005936 beta-Galactosidase Human genes 0.000 description 1
- 108010005774 beta-Galactosidase Proteins 0.000 description 1
- 102000006995 beta-Glucosidase Human genes 0.000 description 1
- 108010047754 beta-Glucosidase Proteins 0.000 description 1
- 230000001588 bifunctional effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 239000001045 blue dye Substances 0.000 description 1
- RSIHSRDYCUFFLA-DYKIIFRCSA-N boldenone Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 RSIHSRDYCUFFLA-DYKIIFRCSA-N 0.000 description 1
- 229940112869 bone morphogenetic protein Drugs 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 235000019835 bromelain Nutrition 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- 229910052793 cadmium Inorganic materials 0.000 description 1
- 239000000298 carbocyanine Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 229960005243 carmustine Drugs 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000004656 cell transport Effects 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 210000003850 cellular structure Anatomy 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- NDAYQJDHGXTBJL-MWWSRJDJSA-N chembl557217 Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](NC(=O)CNC(=O)[C@@H](NC=O)C(C)C)CC(C)C)C(=O)NCCO)=CNC2=C1 NDAYQJDHGXTBJL-MWWSRJDJSA-N 0.000 description 1
- 238000002038 chemiluminescence detection Methods 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 229960001338 colchicine Drugs 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 229960000956 coumarin Drugs 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- DMSZORWOGDLWGN-UHFFFAOYSA-N ctk1a3526 Chemical compound NP(N)(N)=O DMSZORWOGDLWGN-UHFFFAOYSA-N 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- CISNNLXXANUBPI-UHFFFAOYSA-N cyano(nitro)azanide Chemical compound [O-][N+](=O)[N-]C#N CISNNLXXANUBPI-UHFFFAOYSA-N 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- ZPWOOKQUDFIEIX-UHFFFAOYSA-N cyclooctyne Chemical class C1CCCC#CCC1 ZPWOOKQUDFIEIX-UHFFFAOYSA-N 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- GBOGMAARMMDZGR-TYHYBEHESA-N cytochalasin B Chemical compound C([C@H]1[C@@H]2[C@@H](C([C@@H](O)[C@@H]3/C=C/C[C@H](C)CCC[C@@H](O)/C=C/C(=O)O[C@@]23C(=O)N1)=C)C)C1=CC=CC=C1 GBOGMAARMMDZGR-TYHYBEHESA-N 0.000 description 1
- GBOGMAARMMDZGR-JREHFAHYSA-N cytochalasin B Natural products C[C@H]1CCC[C@@H](O)C=CC(=O)O[C@@]23[C@H](C=CC1)[C@H](O)C(=C)[C@@H](C)[C@@H]2[C@H](Cc4ccccc4)NC3=O GBOGMAARMMDZGR-JREHFAHYSA-N 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- RSIHSRDYCUFFLA-UHFFFAOYSA-N dehydrotestosterone Natural products O=C1C=CC2(C)C3CCC(C)(C(CC4)O)C4C3CCC2=C1 RSIHSRDYCUFFLA-UHFFFAOYSA-N 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- ISAOCJYIOMOJEB-UHFFFAOYSA-N desyl alcohol Natural products C=1C=CC=CC=1C(O)C(=O)C1=CC=CC=C1 ISAOCJYIOMOJEB-UHFFFAOYSA-N 0.000 description 1
- 229910003460 diamond Inorganic materials 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- QONQRTHLHBTMGP-UHFFFAOYSA-N digitoxigenin Natural products CC12CCC(C3(CCC(O)CC3CC3)C)C3C11OC1CC2C1=CC(=O)OC1 QONQRTHLHBTMGP-UHFFFAOYSA-N 0.000 description 1
- SHIBSTMRCDJXLN-KCZCNTNESA-N digoxigenin Chemical compound C1([C@@H]2[C@@]3([C@@](CC2)(O)[C@H]2[C@@H]([C@@]4(C)CC[C@H](O)C[C@H]4CC2)C[C@H]3O)C)=CC(=O)OC1 SHIBSTMRCDJXLN-KCZCNTNESA-N 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 239000012039 electrophile Substances 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 108010005965 endoglycoceramidase Proteins 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003344 environmental pollutant Substances 0.000 description 1
- 239000002389 essential drug Substances 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- 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 1
- 229960005420 etoposide Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 102000013165 exonuclease Human genes 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 239000011554 ferrofluid Substances 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 238000002875 fluorescence polarization Methods 0.000 description 1
- MURGITYSBWUQTI-UHFFFAOYSA-N fluorescin Chemical compound OC(=O)C1=CC=CC=C1C1C2=CC=C(O)C=C2OC2=CC(O)=CC=C21 MURGITYSBWUQTI-UHFFFAOYSA-N 0.000 description 1
- 238000005558 fluorometry Methods 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 102000006640 gamma-Glutamyltransferase Human genes 0.000 description 1
- 229940044627 gamma-interferon Drugs 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 108010046301 glucose peroxidase Proteins 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 150000008131 glucosides Chemical class 0.000 description 1
- 229930182480 glucuronide Natural products 0.000 description 1
- 150000008134 glucuronides Chemical class 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 230000037362 glycan biosynthesis Effects 0.000 description 1
- 102000035122 glycosylated proteins Human genes 0.000 description 1
- 108091005608 glycosylated proteins Proteins 0.000 description 1
- 210000002288 golgi apparatus Anatomy 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 235000019382 gum benzoic Nutrition 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000000703 high-speed centrifugation Methods 0.000 description 1
- 229940084986 human chorionic gonadotropin Drugs 0.000 description 1
- 229960002773 hyaluronidase Drugs 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000012216 imaging agent Substances 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229940100601 interleukin-6 Drugs 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 235000011073 invertase Nutrition 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000002605 large molecules Chemical class 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 239000011344 liquid material Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 229960002247 lomustine Drugs 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 229940040129 luteinizing hormone Drugs 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 108010026228 mRNA guanylyltransferase Proteins 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- KNAHXFRERYYDHC-UHFFFAOYSA-N marina blue dye Chemical compound FC1=C(O)C(F)=CC2=C1OC(=O)C(CC(=O)NN)=C2C KNAHXFRERYYDHC-UHFFFAOYSA-N 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
- 229960001924 melphalan Drugs 0.000 description 1
- 229960001428 mercaptopurine Drugs 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 description 1
- 229960004963 mesalazine Drugs 0.000 description 1
- 238000012269 metabolic engineering Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 229960005485 mitobronitol Drugs 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 229940051875 mucins Drugs 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 229940053128 nerve growth factor Drugs 0.000 description 1
- 210000002445 nipple Anatomy 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000006502 nitrobenzyl group Chemical group 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- BRJCLSQFZSHLRL-UHFFFAOYSA-N oregon green 488 Chemical compound OC(=O)C1=CC(C(=O)O)=CC=C1C1=C2C=C(F)C(=O)C=C2OC2=CC(O)=C(F)C=C21 BRJCLSQFZSHLRL-UHFFFAOYSA-N 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- VYNDHICBIRRPFP-UHFFFAOYSA-N pacific blue Chemical compound FC1=C(O)C(F)=C2OC(=O)C(C(=O)O)=CC2=C1 VYNDHICBIRRPFP-UHFFFAOYSA-N 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
- 125000002080 perylenyl group Chemical group C1(=CC=C2C=CC=C3C4=CC=CC5=CC=CC(C1=C23)=C45)* 0.000 description 1
- CSHWQDPOILHKBI-UHFFFAOYSA-N peryrene Natural products C1=CC(C2=CC=CC=3C2=C2C=CC=3)=C3C2=CC=CC3=C1 CSHWQDPOILHKBI-UHFFFAOYSA-N 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- WWBGWPHHLRSTFI-UHFFFAOYSA-N phenalen-1-one Chemical compound C1=CC(C(=O)C=C2)=C3C2=CC=CC3=C1 WWBGWPHHLRSTFI-UHFFFAOYSA-N 0.000 description 1
- NYBYXXFMCVWVHH-UHFFFAOYSA-N phosphanyloxyphosphane Chemical compound POP NYBYXXFMCVWVHH-UHFFFAOYSA-N 0.000 description 1
- XMGBTCJPKKDHPB-UHFFFAOYSA-N phosphanylsulfanylphosphane Chemical compound PSP XMGBTCJPKKDHPB-UHFFFAOYSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- MBWXNTAXLNYFJB-LKUDQCMESA-N phylloquinone Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CCCC(C)CCCC(C)CCCC(C)C)=C(C)C(=O)C2=C1 MBWXNTAXLNYFJB-LKUDQCMESA-N 0.000 description 1
- 239000011772 phylloquinone Substances 0.000 description 1
- QWYZFXLSWMXLDM-UHFFFAOYSA-M pinacyanol iodide Chemical class [I-].C1=CC2=CC=CC=C2N(CC)C1=CC=CC1=CC=C(C=CC=C2)C2=[N+]1CC QWYZFXLSWMXLDM-UHFFFAOYSA-M 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920006122 polyamide resin Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920006254 polymer film Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920005990 polystyrene resin Polymers 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 230000009145 protein modification Effects 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 229950010131 puromycin Drugs 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000006894 reductive elimination reaction Methods 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 125000006853 reporter group Chemical group 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- DYPYMMHZGRPOCK-UHFFFAOYSA-N seminaphtharhodafluor Chemical compound O1C(=O)C2=CC=CC=C2C21C(C=CC=1C3=CC=C(O)C=1)=C3OC1=CC(N)=CC=C21 DYPYMMHZGRPOCK-UHFFFAOYSA-N 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 150000003408 sphingolipids Chemical class 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- PJANXHGTPQOBST-UHFFFAOYSA-N stilbene Chemical compound C=1C=CC=CC=1C=CC1=CC=CC=C1 PJANXHGTPQOBST-UHFFFAOYSA-N 0.000 description 1
- 235000021286 stilbenes Nutrition 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 108060007951 sulfatase Proteins 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 125000003375 sulfoxide group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
- 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 1
- 210000001138 tear Anatomy 0.000 description 1
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide 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](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- 229960002372 tetracaine Drugs 0.000 description 1
- GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 description 1
- QOFZZTBWWJNFCA-UHFFFAOYSA-N texas red-X Chemical compound [O-]S(=O)(=O)C1=CC(S(=O)(=O)NCCCCCC(=O)O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 QOFZZTBWWJNFCA-UHFFFAOYSA-N 0.000 description 1
- 229940126622 therapeutic monoclonal antibody Drugs 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229960003087 tioguanine Drugs 0.000 description 1
- 238000006276 transfer reaction Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- LASOLDQRFPFANT-UHFFFAOYSA-N tris(2-nitrophenyl) phosphate Chemical compound [O-][N+](=O)C1=CC=CC=C1OP(=O)(OC=1C(=CC=CC=1)[N+]([O-])=O)OC1=CC=CC=C1[N+]([O-])=O LASOLDQRFPFANT-UHFFFAOYSA-N 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 238000001419 two-dimensional polyacrylamide gel electrophoresis Methods 0.000 description 1
- 229960003732 tyramine Drugs 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 210000003934 vacuole Anatomy 0.000 description 1
- 239000002435 venom Substances 0.000 description 1
- 231100000611 venom Toxicity 0.000 description 1
- 210000001048 venom Anatomy 0.000 description 1
- 210000000605 viral structure Anatomy 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 229910052726 zirconium Inorganic materials 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
- C12P21/005—Glycopeptides, glycoproteins
-
- 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
- A61K47/54—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 organic compound
- A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/13—Labelling of peptides
-
- 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
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01096—Mannosyl-glycoprotein endo-beta-N-acetylglucosaminidase (3.2.1.96)
-
- 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
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
-
- 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
- G01N33/531—Production of immunochemical test materials
-
- 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
- G01N33/531—Production of immunochemical test materials
- G01N33/532—Production of labelled immunochemicals
-
- 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
- G01N33/531—Production of immunochemical test materials
- G01N33/532—Production of labelled immunochemicals
- G01N33/533—Production of labelled immunochemicals with fluorescent label
-
- 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
- G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
- G01N33/581—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with enzyme label (including co-enzymes, co-factors, enzyme inhibitors or substrates)
-
- 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
- G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
- G01N33/582—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with fluorescent label
-
- 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
- G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
- G01N33/583—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with non-fluorescent dye label
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
- C07K2317/14—Specific host cells or culture conditions, e.g. components, pH or temperature
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
- C07K2317/41—Glycosylation, sialylation, or fucosylation
-
- 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
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
-
- 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
- G01N33/531—Production of immunochemical test materials
- G01N33/532—Production of labelled immunochemicals
- G01N33/534—Production of labelled immunochemicals with radioactive label
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/17—Nitrogen containing
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Analytical Chemistry (AREA)
- Cell Biology (AREA)
- Pathology (AREA)
- Food Science & Technology (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- General Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Tropical Medicine & Parasitology (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Description
本発明は、概して、新規なオリゴ糖結合におけるタンパク質の標識方法、糖鎖を修飾することによる抗体のヒト化方法、並びに修飾されたオリゴ糖と連結されている新規な抗体に関する。
単離若しくは合成されたタンパク質及び抗体(例えばIgG)は、治療用途、診断用途、及び研究用途で用いられている。検出可能な標識(例えばフルオロフォア)で抗体を標識することによって、抗体を、特に標的生体分子又は細胞の検出に用いることができる。抗体に結合性の物質(例えばビオチン)をタグとして結合させてもよく、その結果、それらは特に標的生体分子又は細胞に結合し、更にタグを付与された抗体と結合する物質を用いて(例えばストレプトアビジン)生体分子又は細胞の精製を実施することができる。抗体は通常、システイン若しくはリジン残基(Fabに存在しうる)、又は抗体の結合部位で標識されてもよい。この部位へのタグ又は標識付加により、抗体の結合特性が損なわれるか、又は少なくとも変化しうる。更に、各抗体に結合している標識分子の数を定量することは非常に困難である。
本発明は、概して、新規なオリゴ糖結合におけるタンパク質及び抗体のリモデリング及び標識方法、糖鎖形成を修飾することによる抗体のヒト化方法、並びに修飾されたオリゴ糖に結合する抗体又はタンパク質に関する。なお、抗体又はタンパク質(例えばIgG)は、インビトロ又はインビボでの方法を使用して標識される。
化学ハンドルを含む修飾された糖を、第1のタンパク質上のGlcNAc残基に結合させる工程と、
前記第1のタンパク質を、前記化学ハンドルと反応し得る、リポーター分子、担体分子、又は固体支持体を混合する工程、
を含み、前記リポーター分子、担体分子、又は固体支持体が、前記化学ハンドルの位置でタンパク質と結合し、それにより糖修飾タンパク質が形成される、糖修飾タンパク質の調製方法の提供に関する。
第2のタンパク質上に存在するオリゴ糖を、GlcNAc−GlcNAc結合の位置で切断し、GlcNAc残基を有するオリゴ糖を得る工程と、
前記オリゴ糖を、前記化学ハンドルと反応し得る、リポーター分子、固体支持体、又は担体分子と結合させる工程。
序論:
様々なグリコシダーゼ酵素(エンド−Hなど)は、N結合型オリゴ糖を切断することができ、他の酵素(Gal−Tなど)は、選択されたオリゴ糖を、−OH基を含むアクセプター分子へ転移させることができる。最も効率的なアクセプター分子は、N−アセチルグルコサミン及びグルコースである。あるいは、アクセプター(例えばタンパク質)に対して、選択された糖を代謝的標識により導入することもできる。オリゴ糖を有するタンパク質(例えば治療用抗体)の修飾、又はオリゴ糖を有する固形基質へのタンパク質の接合を含む幾つかの用途へのこの酵素又は代謝系の使用に関して、本明細書に記載する。若干の用途においては、適当なアクセプター分子でコーティングした固体支持体面のための相補的化学ハンドルを有するタンパク質への、オリゴ糖の転移を行ってもよい。更に、検出分子(例えば質量分析による検出、精製及び評価を効率化する、蛍光若しくは蛍光発生化合物、又はタンパク質)へ、糖を転移してもよい。適当なアクセプターOH基に加えて、親和性ペプチドタグ、化学反応性基(active chemical moiety)(例えばアジド、アルキン)又はビオチンを有する大型の分子への転移も可能である。
本発明を詳細に記載する前に、本発明が具体的な組成又は工程に限定されず、適宜変化させることができることを理解すべきである。単数形の「1つの(a)」、「1つの(an)」、「当該(the)」という用語を本明細書及び添付の特許請求の範囲で用いる場合、特に明記しない限りは、複数形をも包含するものとする。すなわち、例えば「リガンド」という用語には複数のリガンドが包含され、「抗体」という用語には複数の抗体が包含される。
抗体及び抗体産生細胞の調製:
本発明のオリゴ糖の切断及び置換に用いられる抗体は、当業者に公知のあらゆる手段を使用して調製することが可能である。抗体産生及び標識のための手順に関する一般的な情報は、例えば、Antibodies:A Laboratory Manual,Cold Spring Harbor Laboratory,Chap.14(1988)に記載されている。インビボでの代謝的標識用の抗体を発現する細胞株は、当業者に公知のあらゆる手段を使用して調製できる。治療用途で、患者に頻繁に投与する場合には、キメラ抗体、ヒト化抗体、及び完全なヒト抗体が好適である。キメラ及びヒト化モノクローナル抗体(ヒト由来及び非ヒト由来の部分を含む)は、標準的な組換えDNA技術を使用して作製することが可能である。係るキメラ及びヒト化モノクローナル抗体は公知技術の組換えDNA技術によって調製することが可能であり、例えば以下の文献に記載されている方法を使用して行ってもよい:Robinsonら、PCT/US86/02269号、Akira,ら、欧州特許出願公開第184,187号、Taniguchi,M.,欧州特許出願公開第171,496号、Morrisonら、欧州特許出願公開第173,494号、Ncubcrgcrら、国際公開第86/01533号、Cabillyら、米国特許第4,816,567号、Cabillyら、欧州特許出願公開第125,023号、Betterら、Science 240:1041−1043(1988)、Liuら、Proc.Natl.Acad.Sci.USA 84:3439−3443(1987)、Liuら、J.Immunol 139:3521−3526(1987)、Sunら、Proc.Natl.Acad.Sci.USA 84:214−218(1987)、Nishimuraら、Canc.Res.47:999−1005(1987)、Woodら、Nature 314:446−449(1985)、及びShawら、J.Natl.Cancer Inst.80:1553−1559(1988)、Morrison,S.L.,Science 229:1202−1207(1985)、Oiら、BioTechniques 4:214(1986)、Winter米国特許第5,225,539号、Jonesら、Nature 321 :552−525(1986)、Verhoeyanら、Science 239:1534、及びBeidlerら、J.Immunol.141:4053−4060(1988)。
本発明の糖タンパク質成分は、いかなる糖タンパク質であってもよく、例えばホルモン、酵素、抗体、ウイルス受容体、ウイルス表層糖タンパク質、寄生体糖タンパク質、寄生体受容体、T細胞受容体、MHC分子、免疫調節因子、腫瘍抗原、ムチン、阻害剤、成長因子、栄養因子、リンホカイン、サイトカイン、トキソイド、神経成長ホルモン、血液凝固因子、接着分子、多剤耐性タンパク質、アデニル酸シクラーゼ、骨形成タンパク質及びレクチンなどが挙げられる。
オリゴ糖は、N−アセチルグルコサミン二糖結合(GlcNac−GlcNac)によって、免疫グロブリンガンマ(IgG)抗体上のアスパラギン残基に結合する。一般に、各IgGは、IgGのネック部の付近に、オリゴ糖がGlcNac−GlcNac結合するための2つの部位を有する。エンドグリコシダーゼ処理(例えばエンドグリコシダーゼH(エンドH))により、2つのGlcNac糖の間が切断される。各糖の切断末端は「還元端」と呼ばれる。オリゴ糖を第1のIgGから切断し、切断されたオリゴ糖を回収することにより、還元端GlcNAcを有するオリゴ糖が得られる。次に、第2のIgGをエンドグリコシダーゼ(例えばエンドH)で処理する。次に、この第2のIgG(還元端を有するGlcNAcを有する)を回収する。次に第1のオリゴ糖に結合しているGlcNAc残基の還元端、及び第2のIgGに結合しているGlcNAc残基オリゴ糖の還元端を処理し、第1のオリゴ糖を第2のIgGに結合させる。
オリゴ糖は、抗体のFc部分上のアスパラギン残基を介してIgGに結合する(図1B)。アミノ酸の位置において、2つのGlcNAc糖は各々β(1−4)結合している。酵素エンド−Hはこの結合を切断し、その結果、1つのGlcNAc残基がIgG上のアスパラギンに結合したままとなり、一方で、もう1つのGlcNacは残りのオリゴ糖に結合したままとなる。オリゴ糖に結合するGlcNAcは反応性の還元端を有し、それは他の糖残基を変質させることなく、選択的に修飾されうる。
酵素ガラクトシルトランスフェラーゼは通常、UDP−ガラクトースから末端GlcNAc残基へガラクトースを転移させる。Khidekelら(J.Am.Chem.Soc.2003,125:16162−16163、Hsieh−Wilson,L.,ら、米国特許出願公開第20050130235,2005年6月16日公開、米国特許出願第10/990,767号)では、変異酵素(Y289L変異体)を用いてアセトン含有ガラクトース基質をGlcNAc残基へ転移させている。アジド含有ガラクトース基質(UDP−GalNAz)は、変異体ガラクトシルトランスフェラーゼによるGlcNAc部位への転移により合成できる。
糖の還元端は、選択的に修飾されうる反応部位である。幾つかの糖(例えばスクロース)は還元端を有さず、遊離還元端を有する糖よりも安定性が高い。酵素エンド−HによるGlcNAc−GlcNAc結合の切断により、オリゴ糖GlcNAcの還元端が露出する。
アジド及び末端のアルキンは、銅触媒の存在下で、環付加反応を受ける。この環付加反応は、例えばSharplessらの方法を使用して実施でき(米国特許出願公開第20050222427号(2005年10月6日公開、PCT/US03/17311号、Lewis W Gら、Angewandte Chemie−Int’l Ed.41(6):1053、method reviewed in Kolb,H.C.,ら、Angew.Chem.Inst.Ed.2001,40:2004−2021)、その反応により、高収率で、かつヘテロ原子結合(炭素−炭素結合ではない)の副反応を生じさせることなく反応するように試薬を変化させ、化学物質のライブラリを調製することが可能となる。金属触媒及び還元剤の存在下で反応を実施する。例えば、Cu(II)を反応系に含有させ、還元剤(例えばアスコルビン酸、金属銅、キノン、ヒドロキノン、ビタミンK1、グルタチオン、システイン、Fe2+、Co2+)の存在下で、電位を印加してもよい。更に好適な還元剤としては、Al、Be、Co、Cr、Fe、Mg、Mn、Ni及びZnからなる群から選択される金属が挙げられる。係る環付加反応を触媒できる他の金属としては、例えばAu、Ag、Hg、Cd、Zr、Ru、Fe、Co、Pt、Pd、Ni、Rh及びWが挙げられる。当業者は、目的のリガンドの使用に応じて適切な金属を決定することができる。
エンドM(又はエンドA)は、グリコシルトランスフェラーゼ活性を有するエンドグリコシダーゼである。エンドHと同様に、当該酵素は2つの残基間の二糖類GlcNAc−GlcNAcを切断する。エンドMは更なる酵素活性を有し、すなわち、当該酵素は、GlcNAc残基を有するオリゴ糖を切断した後で、GlcNAc残基の還元端をOH基に結合させる。すなわち、本発明の他の方法は、切断されたオリゴ糖へのアルキンのインビトロ標識方法の提供に関する。1つの実施形態では、GlcNAc−GlcNAc結合を有するオリゴ糖を有するIgGを、OH−アルキンと共に、エンドMの存在下でインキュベートする。
抗体と、エンド−M又はエンド−Aと、単糖又はオリゴ糖を有するドナーを接触させ、接触溶液を調製する工程であって、当該抗体がアクセプターを有する工程と、
当該接触溶液を充分な時間インキュベートし、アクセプターと単糖又はオリゴ糖との間に共有結合を形成させる工程を含む。
当該治療用抗体と、エンド−M又はエンド−Aと、単糖又はオリゴ糖を有するドナーを接触させ、接触溶液を調製する工程であって、当該抗体がアクセプターを有する工程と、
当該接触溶液を充分な時間インキュベートし、アクセプターと単糖又はオリゴ糖との間に共有結合を形成させる工程と、ヒト化治療用抗体を得る工程を含む。
(a)エンド−M又はエンド−Aと、
(b)オリゴ糖又は単糖を含むドナーと、
(c)検出可能な糖修飾抗体を調製するための取扱説明書を含む。
(a)アクセプターを含有する抗体と、
(b)エンド−M又はエンド−Aと、
(c)オリゴ糖又は単糖を含むドナーと、
(d)溶媒。
インビボでの代謝的標識方法を用いて、抗体産生細胞(例えばハイブリドーマ細胞、及び抗体又は組換え抗体を産生する他の細胞)中で抗体を標識することができる。抗体産生細胞は、非天然の糖基質(例えば反応性化合物/親和性ハンドルを有する非天然の糖基質)を取り込むことができる。化学ハンドルとしては、限定されないが、例えばアジド、トリアリールホスフィン、又はアルキン残基であって、例えば「click」タイプの化学反応に関与できる基が挙げられる。具体的な実施形態では、当該非天然の糖は、細胞への取り込み効率上十分小さい修飾を有するのが好ましい。細胞内の代謝機構により、抗体に結合しているN結合型グリカン又はO結合型グリカンに当該基質が組み込まれる。インビボで標識された抗体が細胞から放出され分離された後、当該標識抗体を、化学ハンドルとの反応性を有する検出/親和性/固定化化合物を使用して直接標識してもよい。これらの化合物としては例えば、限定されないが、フルオロフォア、固体支持体樹脂、マイクロアレイスライド、又は親和性タグなどが挙げられる。
抗体産生細胞を非天然の糖の存在下でインキュベートすることにより、細胞表面糖タンパク質を修飾することができる(例えば米国特許第6,936,701号(Bertozziら)の方法を用いて非天然の糖の存在下で細胞をインキュベートしてもよい)。例えば、細胞を約72時間、非天然の糖(約20mM)とインキュベートする。
反応性化学ハンドルを組み込むことができる非天然の糖基質を合成し、クリック化学反応に用いることができる。アジド/アルキン環付加反応を用いて、親和性プローブ(ビオチン)、色素、ポリマー(例えばポリ(エチレングリコール)若しくはポリデキストラン)、又は他の単糖(例えばグルコース、ガラクトース、フコース、O−GlcNAc、適切な化学ハンドルを有するマンノース由来の糖)を取り込ませることができる。具体的実施形態では、これらのハンドルとしては、例えばアジド、トリアリールホスフィン又はアルキン残基が挙げられる。化学ハンドルはまた、シュタウディンガー反応し得るアジド基であってもよい(Saxon,E.,ら、J.Am.Chem.Soc.,2002,124(50):14893−14902参照)。シュタウディンガー反応は三価のリン化合物と有機アジドとの間の反応を含み(Staudingerら、Hclv.Chim.Acta 1919,2:635)、多くの用途に用いられている(Gololobovら、Tetrahedron 1980,37,437)、(Gololobovら、Tetrahedron 1992,48,1353)。ホスフィンは、隣接アシル基(例えばエステル、チオエステル、又はN−アシルイミダゾール)を有してもよく(すなわちホスフィノエーテル、ホスフィノチオエーテル、ホスフィノイミダゾール)、それによりアザ−イリド中間体をトラップし、加水分解時に安定なアミド結合を形成する。ホスフィンは、典型的にはホスフィンを安定化させる意味でジアリールホスフィン又はトリアリールホスフィンであってもよい。
様々な標識又はタグ(リポーター分子、固体支持体及び担体分子)を、本発明のインビトロ切断オリゴ糖に連結若しくはコンジュゲートさせ、更にそれを本発明に係る切断されたIgGに結合させてもよい。これらの標識又はタグを、代謝的標識の後、細胞から単離したインビボ糖修飾IgGに結合させて標識若しくはタグ付与してもよく、当該標識又はタグは、代謝的標識の間に組み込まれた非天然の糖上の化学/親和性ハンドルと結合させてもよい。
本発明のリポーター分子は、本発明の修飾された糖タンパク質に結合できる、当業者に公知のいかなる直接又は間接的に検出可能なリポーター分子であってもよい。当該リポーター分子としては、クロモフォア、フルオロフォア、蛍光タンパク質、リン光色素、タンデム色素、粒子、ハプテン、酵素、及び放射性同位元素が挙げられるが、これらに限定されない。好適なリポーター分子としては、フルオロフォア、蛍光タンパク質、ハプテン、及び酵素が挙げられる。
第2の組成物中のコンジュゲートの担体分子(又は固体支持体)は、同じ又は異なる分子であってもよい。様々な担体分子の特性に関連する本明細書における考察は、通常、他の実施形態と同様に本発明の本実施形態にも適用できる。
本発明では、種々の固体支持体が利用できる。本発明の使用に適する固体支持体は、典型的には液相において実質的に不溶であり、化学ハンドルと反応し得る置換基を有する。好ましい実施形態では、当該固体支持体は、アルキン又は活性化アルキンを含み、修飾された糖と反応してもよいか、又はその逆であってもよい。本発明の固体支持体は、特定の種類の支持体に限定されず、半固体状の支持体であってもよい。むしろ、当業者に公知の従来技術の多くの支持体が利用できる。すなわち、有用な固体支持体としては、固体及び半固体状のマトリックス(例えばエーロゲル及びヒドロゲル、樹脂、ビーズ、バイオチップ(薄膜コート付きバイオチップなど)、ミクロ流体チップ、シリコンチップ、マルチウェルプレート(またマイクロタイタープレート又はマイクロプレートとも呼ばれる)、膜、導電性及び非伝導性金属、ガラス(顕微鏡スライドガラスなど)、並びに磁性支持体などが挙げられる。有用な固体支持体のより具体的な例としては、シリカゲル、高分子膜、粒子、誘導体化されたプラスチック薄膜、ガラスビーズ、コットン、可塑性ビーズ、アルミナゲル、多糖(例えばセファロース)、ポリ(アクリレート)、ポリスチレン、ポリ(アクリルアミド)、ポリオール、アガロース、アガー、セルロース、デキストラン、デンプン、フィコール、ヘパリン、グリコーゲン、アミロペクチン、マンナン、イヌリン、ニトロセルロース、ジアゾセルロース、ポリ塩化ビニル、ポリプロピレン、ポリエチレン(ポリ(エチレングリコール)など)、ナイロン、ラテックスビーズ、磁気ビーズ、パラ磁性ビーズ、超常磁性ビーズ、デンプンなどが挙げられる。
タンパク質及び抗体のインビボでの代謝的標識に用いるコンポーネントを含むキットもまた提供される。係るキットは、例えば、化学/親和性ハンドル(例えばアジド、トリアリールホスフィン又はアルキン)標識された非天然の糖を含んでもよい。係るキットは更に、例えば、細胞から単離された、代謝的標識された抗体を標識若しくは精製するための試薬を含んでもよい。例えば、キットは、非天然のオリゴ糖(例えばGalNAz、ManNAz又はGlcNAz)を含んでもよい。当該キットは、フルオロフォア標識又は親和性タグ(非天然オリゴ糖上の化学的/親和性ハンドルと反応性を有する)を更に含んでもよい。当業者であれば、例えば、修飾された抗体を標識又はタグ付与するために使用できる様々な標識又はタグ(例えば、限定されないが本明細書において列挙されているもの)を想起すると考えられる。例えば、当該標識又はタグはアルキンと結合でき、それにより、代謝的に標識された抗体上のアジドと接触することでclickタイプの化学反応を行うことができる。
例えば、本発明の方法では、本明細書において記載されているGal−T酵素を用いることにより、糖タンパク質又は抗体上の末端糖残基を直接標識することが可能となる。あるいは、例えばエンド−Hによって糖基を切断し、次に、例えばエンド−M又はエンド−A(両方とも糖の切断及び転移を触媒できる)を用いて、化学ハンドルを含む糖をタンパク質又は抗体に付加させる。他の実施形態では、化学ハンドルを含む糖を、代謝的標識により糖タンパク質又は抗体に付与する。なお、「糖」とは単糖又はオリゴ糖を示す。
第1のタンパク質上に存在するオリゴ糖を、GlcNAc−GlcNAc結合において切断し、還元端を有するGlcNAc残基を含むタンパク質を得る工程と、
化学ハンドルを有する修飾された糖を、前記GlcNAc残基の還元端に結合させる工程と、
前記第1のタンパク質を、前記化学ハンドルと反応し得る標識を有する修飾されたオリゴ糖と混合する工程を含み、
前記修飾されたオリゴ糖は前記化学ハンドルの部位でタンパク質に結合し、それにより糖修飾タンパク質が形成される。
第2のタンパク質上に存在するオリゴ糖をGlcNAc−GlcNAc結合の位置において切断し、還元端を有するGlcNAc残基を有するオリゴ糖を得て、
前記オリゴ糖を、前記化学ハンドルと反応し得る標識を用いて標識することにより得られる。
前記エンドグリコシダーゼMは、前記OH−アルキンを、前記切断されたGlcNAc残基の還元端に結合させ、
前記修飾されたオリゴ糖は、アジド残基で標識されている。
前記第2の抗体の前記切断は、OH−アルキンの存在下で実施され、前記エンドグリコシダーゼMは、前記OH−アルキンを、前記切断されたGlcNAc残基の還元端に結合させ、それによりアルキン修飾されたオリゴ糖が得られ、
前記第1の抗体上の前記修飾された糖上の前記化学ハンドルがアジドである。
モノクローナル及びポリクローナル抗体の、エンドHグリコシダーゼによるオリゴ糖の切断の有無によるHPLC解析
糖鎖除去反応:
90μLの還元及びアルキル化された抗体(1mg/ml)を、40μL 0.5Mクエン酸ナトリウム(pH5.5)及び10μL エンドHf(1,000,000U/mL、New England BioLabs社製)に添加した。密封し、37℃で、48時間インキュベートした。サンプルを遠心分離して沈殿物を除去し、次にHPLC上へ直接注入した。Waters600E LCシステム、Agilent Zorbax 300SB−CNカラム(4.6×150mm、3.5μm)、0.8mL/分の流速で75℃で逆相HPLCを実施した。移動相の組成を、溶媒A:0.1%のTFAを含有する水、及び溶媒B:80%のn−プロパノール、10%のアセトニトリル、10%の0.1%のTFAを含有、とした(条件はRehderら、J.Chrom.A,1102(2006)164−175に記載のものを採用した)。分離は、30分にわたる、20〜40%のBの直線勾配を使用して実施した。結果を図1及び図2に示す。
エンドHグリコシダーゼによるオリゴ糖の切断を伴う及び伴わない、ニワトリ抗ヤギ抗体の酵素標識
ニワトリ抗ヤギIgGを、VivaSpin 5000 MWCOフィルタカラム上で、50mMのMES(pH6.5)バッファーで洗浄した。糖鎖除去のため、1mg/mLの洗浄済IgGのアリコートを、47.5U/μLのエンドH(New England BioLabs社)を含有する50mMのMES(pH6.5)で、37℃で24時間インキュベートした。洗浄済(脱グリコシル化されていない)又は、エンドHf処理されたIgGを更にClick−iT O−GlcNAc酵素標識キットを使用して非変性条件(50mMのMES(pH6.5)中の0.5mg/mlのIgG、120mMのNaCl、11mMのMnCl2、0.1mMのZnCl2、50μMのUDP−GalNAz、5U/mLのAntarcticホスファターゼ、並びに0.65mg/mLのGalT酵素、4℃で一晩インキュベート)でアジド標識した。0.5mLのスピンカラムにパックしたP10サイズ樹脂にサンプルを通し、50mMのトリス(pH8)中に精製した。抗体を含む収集フラクションを、TAMRA Click−iT(商標)検出キット(C33370)で標識し、0.5mLのスピンカラムにパックしたP10サイズ樹脂にサンプルを通し、50mMのトリス(pH8)中に再度精製した。その約250ngを、MOPSバッファーを使用した4〜12%のビス−トリスゲルで分析した。BioRadFXイメージャーで、532nmのレーザー、及び555nmロングパス発光フィルタ使用してゲルをイメージングした(図3A)。SYPRO(登録商標)Rubyプロテインゲル染色を用いてゲルを後染色し、488nmのレーザー及び555nmのロングパス発光フィルタを使用してイメージングした(図3B)。
アジド糖による抗体の代謝的標識
マウスM96ハイブリドーマ細胞を、5日間にわたり、アジド糖アナログ、Ac4GalNAz、Ac4ManNAz、又はAc4GlcNAzで処理した。細胞上清(アジド標識されたモノクローナル抗体を含む)を回収し、タンパク質をクロロホルム/メタノールで沈殿させた。沈殿ペレットを50μLの1%のSDS、100mMのトリス(pH8)で再可溶化し、TAMRA Click−iT(商標)検出キット(C33370)で標識し、1μgを、MOPSバッファーを使用して4〜12%のビス−トリスゲルで分析した。532nmのレーザー及び555nmのロングパス発光フィルタを使用して、BioRadFXイメージャーでゲルをイメージングした(図4A)。SYPRO(登録商標)Rubyプロテインゲル染色でゲルを後染色し、488nmのレーザー及び555nmのロングパス発光フィルタ(図4B)を使用してイメージングした。
代謝的標識及び糖タンパク質サブクラスの「クリック」検出
ジャーカット細胞を、40μM Ac4ManNAz又はAc4GalNAzで3日(A)、又は250μM Ac4GlcNAzで一晩(B)処理した。回収された細胞を50mMのトリスバッファー(プロテアーゼ及びホスファターゼ阻害剤を有する、pH8.0)中で超音波破壊し、ライゼートを高速遠心沈降(100K×g)に供した。ManN Az−及びGalNAz−処理した細胞からの膜ペレットタンパク質、およびGlcNAc−処理細胞からの上清の細胞溶解物をクロロホルム/メタノールにより沈殿させ、界面活性剤で溶解させ、1mMのCuSO4及び5mMのアスコルビン酸(1)の存在下で、蛍光アルキンプローブで標識した。標識され、沈殿させたタンパク質10μgを、1−D NuPAGE(登録商標)Novcx(登録商標)4〜12%ゲル(Invitrogcn社製)で電気泳動に供した。532nmの励起を使用し、Fuji FLA−3000スキャナ(Fuji)によりイメージングした(図5A)。次にゲルをSYPRO(登録商標)Ruby染色(Invitrogen)により後染色し、473nmで励起してイメージングした(図5B)。コントロールのレーンは、未処理細胞(但し蛍光プローブによる処理)の抽出液を表す(図5)。
二次元ゲルによるAc4GlcNAz処理されたジャーカット細胞の可溶性タンパク質の分離
ジャーカット細胞を、250μM Ac4GlcNAz又はDMSO担体(未処理コントロール)と共に一晩培養した。可溶性のライゼートタンパク質を、音波処理及び超遠心分離を用い、実施例4と同様に調製し、蛍光アルキンプローブで1時間標識した。標識されたタンパク質40μgを沈殿させ、7Mの尿素、2Mのチオ尿素、65mMのDTT、2%のCHAPS、1%のZwittergent 3−10、1%のpH3〜10の担体のアンホライトで再度溶解させ、pH3〜10のIEF条片で第1のディメンション、及びMOPSバッファーを有する4−12%のビス−トリスゲルで第2のディメンションで分離した。532nmで励起させたゲルを、SYPRO(登録商標)Ruby染色(Invitrogen)で後染色してイメージングし、更に473nmで励起させ、Fuji FLA−3000スキャナ(Fuji)を使用して再びイメージングした。図6を参照。
40及び50kDのアジド標識されたモデルタンパク質のゲル中検出
1つのN末アジドを有する40及び50kDモデルタンパク質それぞれ25pmolを、ジャーカット細胞ライゼート100μgに取り込ませた(上方パネル)場合と、そうでない場合(下方パネル)を示す。タンパク質を蛍光アルキンプローブで標識し、示すように連続希釈し、NuPAGE(登録商標)Novex(登録商標)4〜12%ゲルで電気泳動した。532nmの励起を行い、FLA−3000スキャナでイメージを得た(左パネル)。ゲルは、それから、SYPRO(登録商標)Ruby染色で染色し、473nmで励起し、イメージングした(右パネル)。標識されたタンパク質の検出感度は10フェムトモル未満であった。図7参照。
40及び50kdのアジド標識モデルタンパク質の標識効率は、複合タンパク質抽出液において不変であった
アジド標識された100ng(25pmol)若しくは10ng(2.5pmol)の各々40Kd及び50Kdタンパク質を、100、50、25、又は0μgコントロールジャーカットライゼート(左パネル)のバックグラウンドにおいて、蛍光アルキンプローブで標識した(標識の後、100μgのコントロールのライゼートを「0ライゼート」に添加し、沈殿による標識タンパク質の回収を促進した)。SYPRO(登録商標)Ruby全タンパク質染色によりゲルを後染色した。図8を参照のこと。
α−クリスタリンO−GlcNAcの酵素的標識及び検出
α−クリスタリンO−GlcNAcを、修飾されたb−GalT1酵素を使用して酵素的にアジド(UDP−GalNAz)標識した。その後、上記のようにタンパク質を蛍光アルキンプローブと反応させた。タンパク質を、示される希釈度で、1−D NuPAGE(登録商標)Novex(登録商標)4−12%ゲルで電気泳動した(2−10%のα−クリスタリンのみを、O−GlcNAc修飾し、それゆえ、O−GlcNAc部分の検出感度は、中程度−低度のフェムトモル範囲(10〜45fmol)であった)。図9を参照。
a−O−GlcNAcモノクローナル抗体CTD110.6と、GalT1酵素標識との比較
Aにおいては、α−クリスタリンO−GlcNAcを、修飾GalT1酵素で酵素的に標識し、ビオチン−アルキンプローブとその後反応させた。タンパク質を、示される希釈度で、1−D NuPAGE(登録商標)Novex(登録商標)4〜12% ビストリスゲルで電気泳動し、PVDF膜上へブロットした。次にPVDF膜をストレプトアビジン−HRPとインキュベートし、タンパク質をECL Plus(商標)(GE Biosystems社製)を使用して検出した。レーン2(NE)は、8pmoLの酵素無添加のコントロールを示す(Aにおいて、ウエスタンブロットによるO−GlcNAcの検出感度は、低度のフェムトモル範囲(3〜10fmol)である)。Bにおいては、無処理のα−クリスタリンを1−Dゲルで電気泳動し、上記の通りブロットした。PVDF膜を、製造者の指示に従い、O−GlcNAcウエスタンブロット検出キット(Pierce社製)を使用して処理した。キットでは、CTD110.6α−O−GlcNAcモノクローナル抗体を利用した。レーン2は、キットに添付のポジティブコントロール(O−GlcNAc−修飾BSA)5ngを含むレーンである。抗体検出系を使用しても、α−クリスタリンは検出されなかった。図10を参照。
同じ二次元ゲルにおける、O−GlcNAcタンパク質、リンタンパク質及び全タンパク質の多重検出:
Ac4GlcNAzでフィードしたジャーカット細胞から可溶性画分を抽出し、2時間にわたり、UV励起性のアルキン色素で標識した。上記のように、クロロホルム/メタノール沈殿させたタンパク質を二次元ゲルで電気泳動した。ゲルを水でリンスし、Lumi−Imager(商標)(Roche社)を用いて、UV照射及び600/bp放出によりイメージングした。次にゲルを、Pro−Q(登録商標)ダイアモンドリンタンパク質染色により染色し、FLA−3000レーザーイメージャーを用いて、532nmの励起/580 LP放出によりイメージングし、SYPRO(登録商標)Ruby全タンパク質染色により染色し、製造者の指示に従い、473nmの励起及び580nmのロングパス放出によって再度イメージングした。図11を参照。
O−GlcNAc修飾タンパク質及びコフィリンの、多重ウエスタンブロット検出
ジャーカット細胞の可溶性タンパク質25μgを上記のとおり二次元ゲル電気泳動に供し、更にPVDF膜にブロットした。PVDF膜は、α−コフィリンポリクローナル抗体とインキュベートし、更にGAR−HRP二次抗体を用い、ECL Plus(商標)検出(GE Biosystems社製)によって検出した。イメージング後、ブロット膜を、ストレプトアビジンAPとインキュベートし、O−GlcNAcタンパク質を、WesternBreeze(登録商標)化学発光検出キット(Invitrogen社製)を使用して検出した。図12を参照。
コントロール及び阻害剤処理された培養細胞抽出液における、O−GlcNAc修飾タンパク質のディファレンシャル検出
ジャーカット細胞をAc4GlcNAzで一晩培養し、PUGNAc処理の有無に関して解析した。PUGNAcは、一般的に用いられるO−GlcNAcアーゼの阻害剤である。可溶性のジャーカットライゼートを、蛍光アルキンで標識した。レーン1)回収前の3時間、50μM PUGNAc及び4mMのグルコサミンで処理した細胞、レーン2)無処理、レーン3から5)250μM Ac4GlcNAzで一晩培養した細胞、レーン6から8)250μM Ac4GlcNAzで一晩培養し、更に回収前の3時間、50μM PUGNAc及び更に250μM Ac4GlcNAzで処理した細胞、PUGNAcで処理したタンパク質(レーン6−8)は、未処理のコントロール(レーン3−5)よりも、O−GlcNAc染色の顕著な増加を示した。図13を参照。
糖タンパク質のゲル中での連結
ゲル中での連結に用いる蛍光アルキン化合物を、図18(AからD)に示す。更に、2つの強力な蛍光発生アルキンをE及びFに示す。TAMRA−アルキン化合物(上の左側フレームに示す)をゲル中染色試験に用い、反応性のアジド−スクシンイミジルエステルを使用してインビトロで、又はフィード細胞にアジド修飾した糖をフィードしてインビボで、アジド基をタンパク質に組み込ませた。
アジドオボアルブミン及びアジド−ミオグロビンをそれぞれ2.5μgずつ用い、80μgの非標識ジャーカットライゼートにスパイクした。次にライゼートを2時間にわたり、TAMRAアルキンで標識した。反応液の組成は、50mMトリス(pH8)、25%のプロピレングリコール、1mM CuSO4、5mMのアスコルビン酸ナトリウム、20μM TAMRAアルキンとした。キレーター(10mMのTPEN、EDTA、バトクプロイン二スルホン酸(BCS)又はネオクプロインのいずれか)を伴うおよび伴わない反応を実施した。コントロール反応を、CuSO4なしで実施した。標識後、サンプルを沈殿させ、各サンプル約30μgを、7mMの尿素/2mMのチオ尿素/65mMのDTT/2%のCHAPS/中に再度溶解させ、二次元ゲル(pH4〜7、IEF条片、MOPSバッファーを含む4〜12%のビストリスゲル)で分析した。TAMRAシグナルを、Fuji FLA3000を使用して、532nmの励起、580のロングパス放出によりイメージングし、更にゲルをSYPRO(登録商標)Ruby全タンパク質ゲル染色で後染色した(図14A)。その結果、キレーターの添加により、タンパク質分離の解像度が改善され、特にバトクプロイン二スルホン酸(BCS)、Cu(I)キレーターでは最高の結果が得られた。全タンパク質染色(図14B)を参照。
Click化学反応を用いた抗体の酵素的標識
ヤギIgG抗体を還元し、アルキル化し、更に2つの別々のアリコートに分け、エンドH酵素を使用して脱グリコシル化した。脱グリコシル化された抗体(2つの別々の調製物)を更に150μL反応液中で、33ng/μLのGalT1(Y289L)酵素及び500μMのUDP−GalNAz(0.5μg/μLヤギ抗体)を使用して、GalNAz標識した。反応液を4℃で一晩インキュベートした。4〜500ngのヤギ抗体(図示するゲルを参照、GalNAzを含まないコントロールか、又はアジド標識)を、4〜12%のビストリスゲルの各レーンにロードした。MESバッファーを使用して、200vで〜50分間、電気泳動を実施した。ゲルをTAMRA−アルキン染色し、532nm(励起)及び580nmの放出により、Fuji imagerを用いてイメージングした。一晩用のプロトコルを使用して、SYPRO Rubyによってゲルを後染色した。図17を参照。
Claims (14)
- Y289L変異体ガラクトシルトランスフェラーゼを用いて、アジド修飾された糖を、第1のタンパク質上のGlcNAc残基に結合させる工程と、
前記アジド修飾された糖が結合した第1のタンパク質を、前記アジド修飾された糖と反応し得る、リポーター分子、担体分子、又は固体支持体と混合する工程と、
を含む、糖修飾タンパク質の調製方法であって、
前記アジド修飾された糖が、UDP−GalNAzであり、かつ、前記リポーター分子、担体分子、又は固体支持体が、アルキン又は活性化アルキン基で標識されており、かつ、
前記リポーター分子、担体分子、又は固体支持体が、前記アルキン又は活性化アルキン基を介して前記アジド修飾された糖のアジド基の位置でタンパク質に結合し、それにより糖修飾タンパク質が形成される、方法。 - 前記第1のタンパク質が抗体である、請求項1記載の方法。
- 前記結合工程の前に、第1のタンパク質上に存在するオリゴ糖をGlcNAc−GlcNAc結合の位置で切断し、GlcNAc残基を含むタンパク質を得る工程であって、任意に、該オリゴ糖が、GlcNAc−GlcNAc結合の位置におけるエンドグリコシダーゼH切断、またはGlcNAc−GlcNAc結合の位置におけるエンドグリコシダーゼM切断を用いて切断され、その後に前記オリゴ糖が第1のタンパク質へ転移する、工程を含む、請求項1または2記載の方法。
- 以下の工程を更に含む、請求項1または2記載の方法:
第2のタンパク質上に存在するオリゴ糖を、GlcNAc−GlcNAc結合の位置で切断し、GlcNAc残基を有するオリゴ糖を得る工程と、
前記オリゴ糖を、前記化学ハンドルと反応し得る、リポーター分子、固体支持体、又は担体分子と結合させる工程。 - GlcNAc残基を有する前記オリゴ糖が重炭酸アンモニウムで処理され、かつ前記オリゴ糖がスクシンイミジルエステルによってアルキンに結合される、請求項4記載の方法。
- 前記第2のタンパク質が、前記第1のタンパク質と異なる細胞株又は異なる種類の細胞中で合成される、請求項4記載の方法。
- 前記第2のタンパク質が、ヒト細胞中で合成される、請求項4記載の方法。
- 前記リポーター分子が、蛍光色素、酵素、放射標識、金属キレーター、又は検出可能な基質からなる群から選択される、請求項1または2記載の方法。
- 前記担体分子が、治療薬、DNA、タンパク質、ペプチド、及び糖からなる群から選択される、請求項1または2記載の方法。
- 前記糖修飾タンパク質が、修飾される前の第1のタンパク質と比較して、抗原性がより強くなるか又は弱くなる、請求項1または2記載の方法。
- 前記第1のタンパク質が、非ヒト供給源由来である、請求項1または2記載の方法。
- 前記糖修飾タンパク質がヒト化されている、請求項1または2記載の方法。
- 前記結合工程が、プロテアーゼを実質的に含まない溶液中で実施される、請求項1または2記載の方法。
- 請求項2〜13のいずれか一項記載の方法により得られた、標識されたオリゴ糖を含む抗体。
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US77222106P | 2006-02-10 | 2006-02-10 | |
US60/772,221 | 2006-02-10 | ||
US80464006P | 2006-06-13 | 2006-06-13 | |
US60/804,640 | 2006-06-13 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014209061A Division JP2015044828A (ja) | 2006-02-10 | 2014-10-10 | オリゴ糖によるタンパク質の修飾及び標識方法 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018122653A Division JP2018158943A (ja) | 2006-02-10 | 2018-06-28 | オリゴ糖によるタンパク質の修飾及び標識方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2016190863A JP2016190863A (ja) | 2016-11-10 |
JP6646537B2 true JP6646537B2 (ja) | 2020-02-14 |
Family
ID=38440198
Family Applications (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008553858A Pending JP2009528988A (ja) | 2006-02-10 | 2007-02-12 | 翻訳後修飾されたタンパク質の標識及び検出方法 |
JP2014209061A Withdrawn JP2015044828A (ja) | 2006-02-10 | 2014-10-10 | オリゴ糖によるタンパク質の修飾及び標識方法 |
JP2016129992A Active JP6646537B2 (ja) | 2006-02-10 | 2016-06-30 | オリゴ糖によるタンパク質の修飾及び標識方法 |
JP2018122653A Pending JP2018158943A (ja) | 2006-02-10 | 2018-06-28 | オリゴ糖によるタンパク質の修飾及び標識方法 |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008553858A Pending JP2009528988A (ja) | 2006-02-10 | 2007-02-12 | 翻訳後修飾されたタンパク質の標識及び検出方法 |
JP2014209061A Withdrawn JP2015044828A (ja) | 2006-02-10 | 2014-10-10 | オリゴ糖によるタンパク質の修飾及び標識方法 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018122653A Pending JP2018158943A (ja) | 2006-02-10 | 2018-06-28 | オリゴ糖によるタンパク質の修飾及び標識方法 |
Country Status (5)
Country | Link |
---|---|
US (10) | US8716033B2 (ja) |
EP (7) | EP2623986B1 (ja) |
JP (4) | JP2009528988A (ja) |
DK (3) | DK1991273T4 (ja) |
WO (2) | WO2008029281A2 (ja) |
Families Citing this family (119)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK1991273T4 (da) | 2006-02-10 | 2022-02-07 | Life Technologies Corp | Mærkning og påvisning af post-translationelt modificerede proteiner |
US20090214439A1 (en) * | 2006-03-15 | 2009-08-27 | Trustees Of Tufts College | Fluorinated Carbohydrates and Their Use in Tumor Visualization, Tissue Engineering, and Cancer Chemotherapy |
US8034396B2 (en) * | 2008-04-01 | 2011-10-11 | Tyco Healthcare Group Lp | Bioadhesive composition formed using click chemistry |
AU2009242453B2 (en) | 2008-05-02 | 2014-12-04 | Seagen Inc. | Methods and compositions for making antibodies and antibody derivatives with reduced core fucosylation |
JP5569768B2 (ja) * | 2008-12-02 | 2014-08-13 | 国立大学法人九州大学 | ヌクレオシド三リン酸誘導体、核酸プローブ、マルチラベル化核酸プローブおよび標的核酸の検出方法 |
EP4212541A1 (en) | 2008-12-16 | 2023-07-19 | Genzyme Corporation | Oligosaccharide-protein conjugates and their intermediates |
WO2010091142A1 (en) * | 2009-02-04 | 2010-08-12 | President And Fellows Of Harvard College | Compositions and methods for labeling and imaging phospholipids |
SG10201406505WA (en) * | 2009-02-14 | 2014-11-27 | Genentech Inc | Methods for the detection of fatty-acylated proteins |
US8968733B2 (en) * | 2009-02-21 | 2015-03-03 | Sofradim Production | Functionalized surgical adhesives |
US8956603B2 (en) | 2009-02-21 | 2015-02-17 | Sofradim Production | Amphiphilic compounds and self-assembling compositions made therefrom |
US8877170B2 (en) * | 2009-02-21 | 2014-11-04 | Sofradim Production | Medical device with inflammatory response-reducing coating |
AU2010215936B2 (en) | 2009-02-21 | 2015-03-05 | Covidien Lp | Medical devices having activated surfaces |
AU2010215199B2 (en) | 2009-02-21 | 2015-01-15 | Sofradim Production | Compounds and medical devices activated with solvophobic linkers |
US8663689B2 (en) | 2009-02-21 | 2014-03-04 | Sofradim Production | Functionalized adhesive medical gel |
US9555154B2 (en) | 2009-02-21 | 2017-01-31 | Covidien Lp | Medical devices having activated surfaces |
US8535477B2 (en) * | 2009-02-21 | 2013-09-17 | Sofradim Production | Medical devices incorporating functional adhesives |
US9523159B2 (en) | 2009-02-21 | 2016-12-20 | Covidien Lp | Crosslinked fibers and method of making same using UV radiation |
AU2010215194A1 (en) | 2009-02-21 | 2011-10-13 | Sofradim Production | Apparatus and method of reacting polymers passing through metal ion chelated resin matrix to produce injectable medical devices |
US9375699B2 (en) | 2009-02-21 | 2016-06-28 | Sofradim Production | Apparatus and method of reacting polymers by exposure to UV radiation to produce injectable medical devices |
EP2398941B1 (en) | 2009-02-21 | 2016-07-13 | Sofradim Production | Crosslinked fibers and method of making same by extrusion |
WO2010095056A2 (en) | 2009-02-21 | 2010-08-26 | Sofradim Production | Medical devices with an activated coating |
US8512728B2 (en) | 2009-02-21 | 2013-08-20 | Sofradim Production | Method of forming a medical device on biological tissue |
EP2253635B1 (en) | 2009-04-28 | 2014-03-19 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Novel hydrophilic and lipophilic rhodamines for labelling and imaging |
WO2010149190A1 (en) * | 2009-06-26 | 2010-12-29 | Max-Planck-Gesellschaft Zur | Novel fluorinated rhodamines as photostable fluorescent dyes for labelling and imaging techniques |
US8440905B2 (en) * | 2009-09-25 | 2013-05-14 | Robert J. LeSuer | Copper complex dye sensitized solar cell |
CN106519588B (zh) | 2009-11-09 | 2019-08-20 | 华盛顿大学商业化中心 | 官能化发色聚合物点及其生物共轭体 |
US9090542B2 (en) * | 2009-11-11 | 2015-07-28 | University Of Georgia Research Foundation, Inc. | Methods for labeling a substrate using a hetero-diels-alder reaction |
US20110108411A1 (en) * | 2009-11-11 | 2011-05-12 | Popik Vladimir V | Methods for labeling a substrate using a hetero-diels-alder reaction |
US20110129834A1 (en) * | 2009-11-24 | 2011-06-02 | Life Technologies Corporation | Selective amplification of polynucleotide sequences |
WO2011117745A2 (en) | 2010-03-25 | 2011-09-29 | Sofradim Production | Surgical fasteners and methods for sealing wounds |
WO2011117744A2 (en) | 2010-03-25 | 2011-09-29 | Sofradim Production | Medical devices incorporating functional adhesives |
AU2011276443A1 (en) | 2010-06-29 | 2013-01-31 | Covidien Lp | Microwave-powered reactor and method for in situ forming implants |
US8865857B2 (en) | 2010-07-01 | 2014-10-21 | Sofradim Production | Medical device with predefined activated cellular integration |
WO2012014080A2 (en) | 2010-07-27 | 2012-02-02 | Sofradim Production | Polymeric fibers having tissue reactive members |
US20120028335A1 (en) | 2010-07-28 | 2012-02-02 | Life Technologies Corporation | Anti-viral azide-containing compounds |
CN103237546B (zh) * | 2010-07-28 | 2016-06-08 | 生命科技公司 | 抗病毒的含有叠氮化物的化合物 |
AU2011285490B2 (en) | 2010-08-05 | 2016-04-21 | Seagen Inc. | Methods of inhibition of protein fucosylation in vivo using fucose analogs |
EP2944605B1 (en) | 2010-10-18 | 2018-12-05 | University of Washington through its Center for Commercialization | Chromophoric polymer dots |
EP2714731A1 (en) * | 2011-05-31 | 2014-04-09 | ProBioGen AG | Methods for preparation of fucose-linked site specific conjugates of proteins with toxins, adjuvants, detection labels and pharmacokinetic half life extenders |
WO2013056720A1 (en) | 2011-10-18 | 2013-04-25 | Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften E.V. | Fluorescent dyes with phosphorylated hydroxymethyl groups and their use in light microscopy and imaging techniques |
US9797840B2 (en) | 2011-11-28 | 2017-10-24 | University Of Washington Through Its Center For Commercialization | Highly fluorescent polymer nanoparticle |
US9717803B2 (en) * | 2011-12-23 | 2017-08-01 | Innate Pharma | Enzymatic conjugation of polypeptides |
WO2013101902A2 (en) | 2011-12-30 | 2013-07-04 | University Of Washington, Through Its Center For Commercialization | Chromophoric polymer dots with narrow-band emission |
US20150017703A1 (en) * | 2012-01-26 | 2015-01-15 | Life Technologies Corporation | Methods for increasing the infectivity of viruses |
WO2013116614A1 (en) | 2012-02-03 | 2013-08-08 | University Of Washington Through Its Center For Commercialization | Polyelectrolyte-coated polymer dots and related methods |
ES2678211T3 (es) | 2012-03-27 | 2018-08-09 | Ventana Medical Systems, Inc. | Conjugados de señalización y procedimientos de uso |
EP2887947B1 (en) | 2012-08-23 | 2019-06-05 | Seattle Genetics, Inc. | Fucose analogues for the treatment of sickle cell disease |
EP2911699B1 (en) | 2012-10-23 | 2017-11-15 | SynAffix B.V. | Modified antibody, antibody-conjugate and process for the preparation thereof |
WO2014066733A2 (en) * | 2012-10-25 | 2014-05-01 | Life Technologies Corporation | Methods and compositions for enzyme-mediated site-specific radiolabeling of glycoproteins |
CN104007091A (zh) * | 2013-02-26 | 2014-08-27 | 中国科学院天津工业生物技术研究所 | 一种基于液滴微流控芯片的微生物高通量检测*** |
JP6587605B2 (ja) | 2013-03-14 | 2019-10-09 | ユニバーシティ オブ ワシントン スルー イッツ センター フォー コマーシャリゼーション | ポリマードット組成物および関連方法 |
LT2991683T (lt) * | 2013-05-02 | 2019-12-27 | Glykos Finland Oy | Glikoproteino arba glikano konjugatai su toksine medžiaga |
WO2014197547A1 (en) * | 2013-06-04 | 2014-12-11 | Tribiotica Llc | Methods and compositions for templated assembly of nucleic acid specific heterocompounds |
US9775928B2 (en) | 2013-06-18 | 2017-10-03 | Covidien Lp | Adhesive barbed filament |
WO2015057064A1 (en) | 2013-10-14 | 2015-04-23 | Synaffix B.V. | Modified glycoprotein, protein-conjugate and process for the preparation thereof |
EP3057618B1 (en) | 2013-10-14 | 2022-12-14 | SynAffix B.V. | Glycoengineered antibody, antibody-conjugate and methods for their preparation |
JP2016538877A (ja) | 2013-10-14 | 2016-12-15 | シンアフィックス ビー.ブイ. | 修飾糖タンパク質、タンパク質コンジュゲート及びそれらの調製方法 |
WO2015057066A1 (en) | 2013-10-14 | 2015-04-23 | Synaffix B.V. | Glycoengineered antibody, antibody-conjugate and methods for their preparation |
CN103604791B (zh) * | 2013-11-29 | 2016-01-20 | 广西师范大学 | 一种测定叠氮离子的荧光光谱方法 |
JP2017505770A (ja) | 2014-01-24 | 2017-02-23 | シンアフィックス ビー.ブイ. | (ヘテロ)アリール1,3−双極子化合物と(ヘテロ)シクロアルキンとの環化付加のためのプロセス |
EP3097080A1 (en) | 2014-01-24 | 2016-11-30 | SynAffix B.V. | Process for the cycloaddition of a halogenated 1,3-dipole compound with a (hetero)cycloalkyne |
US20170009266A1 (en) | 2014-01-24 | 2017-01-12 | Synaffix B.V. | Process for the attachment of a galnac moiety comprising a (hetero)aryl group to a glcnac moiety, and product obtained thereby |
JP5847213B2 (ja) * | 2014-02-06 | 2016-01-20 | ホーユー株式会社 | 2次元電気泳動方法 |
WO2015156264A1 (ja) * | 2014-04-08 | 2015-10-15 | 国立大学法人弘前大学 | 新規なグルコース誘導体、および該誘導体を用いた細胞イメージング方法およびイメージング剤 |
WO2015157446A1 (en) | 2014-04-08 | 2015-10-15 | University Of Georgia Research Foundation Inc. | Site-specific antibody-drug glycoconjugates and methods |
CN107109454A (zh) | 2014-08-04 | 2017-08-29 | 西纳福克斯股份有限公司 | 用β‑(1,4)‑N‑乙酰半乳糖胺转移酶或其突变体修饰糖蛋白的方法 |
US20160130324A1 (en) | 2014-10-31 | 2016-05-12 | Shire Human Genetic Therapies, Inc. | C1 Inhibitor Fusion Proteins and Uses Thereof |
EP3227476B1 (en) | 2014-12-02 | 2021-02-24 | Tribiotica Llc | Methods and kits for theranostic applications |
CN104761726B (zh) * | 2015-01-08 | 2020-05-22 | 湖南工业大学 | 一种基于主链长度调控乙基纤维素接枝聚苯乙烯共聚物材料有序孔孔径的方法 |
NO3134520T3 (ja) | 2015-04-23 | 2018-05-19 | ||
AU2016353466B2 (en) * | 2015-11-10 | 2020-10-01 | Eth Zurich | Tri-functional crosslinking reagents |
CA3005906A1 (en) | 2015-11-19 | 2017-05-26 | Shire Human Genetic Therapies, Inc. | Recombinant human c1 esterase inhibitor and uses thereof |
CN105399639A (zh) * | 2015-12-14 | 2016-03-16 | 天津科技大学 | 一种酪胺人工抗原和抗体及其制备方法与应用 |
EP3413922A1 (en) | 2016-02-08 | 2018-12-19 | SynAffix B.V. | Improved sulfamide linkers for use in bioconjugates |
US11951175B2 (en) | 2016-02-08 | 2024-04-09 | Synaffix B.V. | Bioconjugates containing sulfamide linkers for use in treatment |
CN109069658B (zh) * | 2016-02-08 | 2022-10-14 | 西纳福克斯股份有限公司 | 用于靶向her2肿瘤的具有改善的治疗指数的抗体-缀合物以及用于改善抗体-缀合物的治疗指数的方法 |
EP3414328B1 (en) | 2016-02-08 | 2024-01-10 | Synaffix B.V. | Enzymes for trimming of glycoproteins |
JP7084320B2 (ja) * | 2016-06-15 | 2022-06-14 | ザ ジェネラル ホスピタル コーポレイション | 生体直交型反応を用いた生体材料の代謝標識及び分子増強 |
EP3472210A1 (en) * | 2016-06-17 | 2019-04-24 | Life Technologies Corporation | Site-specific crosslinking of antibodies |
US10723760B2 (en) * | 2016-09-02 | 2020-07-28 | Korea Advanced Institute Of Science And Technology | Method for preparing site-specifically modified protein based on novel carbon-carbon bond formation |
WO2018044130A1 (ko) * | 2016-09-02 | 2018-03-08 | 한국과학기술원 | 새로운 탄소-탄소 결합 기반 위치 특이적으로 변형된 단백질의 제조방법 |
CN110121559A (zh) | 2016-11-21 | 2019-08-13 | 特里比奥迪卡有限责任公司 | 通过模板化组装反应进行蛋白质的定向折叠组装或二聚化的方法 |
EP3541952A4 (en) | 2016-11-21 | 2020-06-24 | Tribiotica Llc | METHOD FOR PREVENTING THE TITRATION OF BIMOLECULAR TEMPLATE REACTIONS BY STRUCTURALLY DETERMINED DIFFERENTIAL HYBRIDIZATIONS |
US11085062B2 (en) | 2016-12-29 | 2021-08-10 | Development Center For Biotechnology | Processes for preparing glycoprotein-drug conjugates |
CN108264372B (zh) * | 2016-12-30 | 2021-08-24 | 四川大学 | 高强度、低导热的a级不燃气凝胶型泡沫及其制备和应用 |
CN108728397B (zh) * | 2017-04-17 | 2022-05-20 | 中国科学院微生物研究所 | 对昆虫蛋白或昆虫表达***表达的外源蛋白进行标记的方法 |
CA3062238A1 (en) | 2017-05-11 | 2018-11-15 | Vib Vzw | Glycosylation of variable immunoglobulin domains |
WO2018237334A1 (en) * | 2017-06-23 | 2018-12-27 | The Scripps Research Institute | LYSINE-REACTIVE PROBES AND USES THEREOF |
CN107486270B (zh) * | 2017-08-08 | 2020-10-23 | 上海格荣生物科技有限公司 | 基于球-刷双层纳米结构基底微阵列芯片的制备方法 |
CN110093303A (zh) * | 2018-01-29 | 2019-08-06 | 浙江千禾生物科技有限公司 | 一种半固体培养基及其应用 |
CN112672764A (zh) | 2018-06-19 | 2021-04-16 | 格莱科斯生物医药公司 | 结合物 |
CN112672765A (zh) | 2018-06-29 | 2021-04-16 | 格莱科斯生物医药公司 | 结合物 |
US11911484B2 (en) | 2018-08-02 | 2024-02-27 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating myotonic dystrophy |
US12018087B2 (en) | 2018-08-02 | 2024-06-25 | Dyne Therapeutics, Inc. | Muscle-targeting complexes comprising an anti-transferrin receptor antibody linked to an oligonucleotide and methods of delivering oligonucleotide to a subject |
US11168141B2 (en) | 2018-08-02 | 2021-11-09 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating dystrophinopathies |
JP2021533200A (ja) | 2018-08-02 | 2021-12-02 | ダイン セラピューティクス, インコーポレーテッドDyne Therapeutics, Inc. | 顔面・肩甲・上腕筋ジストロフィーを処置するための筋標的化複合体およびそれらの使用 |
SG11202100934PA (en) | 2018-08-02 | 2021-02-25 | Dyne Therapeutics Inc | Muscle targeting complexes and uses thereof for treating dystrophinopathies |
CN109316463B (zh) * | 2018-08-03 | 2021-03-19 | 暨南大学 | 一种复合纳米粒及其制备方法和应用 |
WO2020094670A1 (en) | 2018-11-05 | 2020-05-14 | Synaffix B.V. | Antibody-conjugates for targeting of tumours expressing trop-2 |
GB201901608D0 (en) | 2019-02-06 | 2019-03-27 | Vib Vzw | Vaccine adjuvant conjugates |
MX2021009987A (es) * | 2019-02-20 | 2021-11-04 | Diamidex | Metodos para el etiquetado de celulas eucariotas de un organismo multicelular utilizando compuestos monosacaridos modificados. |
AU2020274563A1 (en) * | 2019-05-13 | 2021-12-09 | Shanghai Polaris Biology Co., Ltd. | A tag for labeling biomolecules |
GB201918279D0 (en) | 2019-12-12 | 2020-01-29 | Vib Vzw | Glycosylated single chain immunoglobulin domains |
US20230038373A1 (en) | 2019-12-18 | 2023-02-09 | Glykos Biomedical Oy | Stabile conjugate |
US11969475B2 (en) | 2021-07-09 | 2024-04-30 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating facioscapulohumeral muscular dystrophy |
US11633498B2 (en) | 2021-07-09 | 2023-04-25 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating myotonic dystrophy |
US11638761B2 (en) | 2021-07-09 | 2023-05-02 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating Facioscapulohumeral muscular dystrophy |
US11771776B2 (en) | 2021-07-09 | 2023-10-03 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating dystrophinopathies |
US11672872B2 (en) | 2021-07-09 | 2023-06-13 | Dyne Therapeutics, Inc. | Anti-transferrin receptor antibody and uses thereof |
TW202334429A (zh) | 2021-10-01 | 2023-09-01 | 中央研究院 | Sars-cov-2棘蛋白特異性抗體及其用途 |
GB202116442D0 (en) * | 2021-11-15 | 2021-12-29 | Actome Gmbh | High-efficacy labeling of antibodies with oligonucleotide labels |
WO2023180490A1 (en) | 2022-03-23 | 2023-09-28 | Synaffix B.V. | Antibody-conjugates for targeting of tumours expressing nectin-4 |
WO2023180485A1 (en) | 2022-03-23 | 2023-09-28 | Synaffix B.V. | Antibody-conjugates for targeting of tumours expressing trop-2 |
WO2023180489A1 (en) | 2022-03-23 | 2023-09-28 | Synaffix B.V. | Antibody-conjugates for targeting of tumours expressing carcinoembyronic antigen |
WO2023180484A1 (en) | 2022-03-23 | 2023-09-28 | Synaffix B.V. | Antibody-conjugates for targeting of tumours expressing ptk7 |
US11931421B2 (en) | 2022-04-15 | 2024-03-19 | Dyne Therapeutics, Inc. | Muscle targeting complexes and formulations for treating myotonic dystrophy |
EP4285934A1 (en) | 2022-05-30 | 2023-12-06 | CER Groupe | Modified trimannose-oligosacharides, bisected n-glycans comprising said trimannose core and method for obtaining them |
CN115656350A (zh) * | 2022-09-05 | 2023-01-31 | 华熙生物科技股份有限公司 | 一种确定交联透明质酸的修饰位点和交联方式的方法 |
CN115951070A (zh) * | 2023-01-19 | 2023-04-11 | 北京青莲百奥生物科技有限公司 | 一种检测样品中的蛋白的方法 |
Family Cites Families (130)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US527027A (en) * | 1894-10-02 | Method of and apparatus for producing letters or characters in bread | ||
US4196265A (en) | 1977-06-15 | 1980-04-01 | The Wistar Institute | Method of producing antibodies |
JPS6033479B2 (ja) | 1980-07-30 | 1985-08-02 | 協和醗酵工業株式会社 | 過酸化水素の定量方法 |
US4711955A (en) | 1981-04-17 | 1987-12-08 | Yale University | Modified nucleotides and methods of preparing and using same |
US4520110A (en) | 1981-10-06 | 1985-05-28 | The Board Of Trustees Of The Leland Stanford Junior University | Fluorescent immunoassay employing a phycobiliprotein labeled ligand or receptor |
US4859582A (en) | 1981-10-06 | 1989-08-22 | The Board Of Trustees Of The Leland Stanford Jr. University | Fluorescent conjugates for analysis of molecules and cells |
US5055556A (en) | 1981-10-06 | 1991-10-08 | The Board Of Trustees Of The Leland Stanford Jr. Univ. | Fluorescent conjugates for analysis of molecules and cells |
US4542104A (en) | 1983-04-06 | 1985-09-17 | The Board Of Trustees Of The Leland Stanford Jr. Univ. | Phycobiliprotein fluorescent conjugates |
US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
JPS6147500A (ja) | 1984-08-15 | 1986-03-07 | Res Dev Corp Of Japan | キメラモノクロ−ナル抗体及びその製造法 |
EP0173494A3 (en) | 1984-08-27 | 1987-11-25 | The Board Of Trustees Of The Leland Stanford Junior University | Chimeric receptors by dna splicing and expression |
GB8422238D0 (en) | 1984-09-03 | 1984-10-10 | Neuberger M S | Chimeric proteins |
US4603209A (en) | 1984-09-07 | 1986-07-29 | The Regents Of The University Of California | Fluorescent indicator dyes for calcium ions |
JPS61134325A (ja) | 1984-12-04 | 1986-06-21 | Teijin Ltd | ハイブリツド抗体遺伝子の発現方法 |
FR2574415B1 (fr) * | 1984-12-11 | 1987-05-29 | Rhone Poulenc Spec Chim | Copolyetheramides techniques souples a basse temperature |
US4714763A (en) | 1985-07-11 | 1987-12-22 | Viomedics Inc. | Novel oxazine-ureas and thiazine urea chromophors as fluorescent labels |
US4676980A (en) | 1985-09-23 | 1987-06-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Target specific cross-linked heteroantibodies |
US4812409A (en) | 1986-01-31 | 1989-03-14 | Eastman Kodak Company | Hydrolyzable fluorescent substrates and analytical determinations using same |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
US5627027A (en) | 1986-04-18 | 1997-05-06 | Carnegie Mellon University | Cyanine dyes as labeling reagents for detection of biological and other materials by luminescence methods |
US5569587A (en) * | 1986-04-18 | 1996-10-29 | Carnegie Mellon University | Method for labeling and detecting materials employing luminescent arysulfonate cyanine dyes |
US5268486A (en) * | 1986-04-18 | 1993-12-07 | Carnegie-Mellon Unversity | Method for labeling and detecting materials employing arylsulfonate cyanine dyes |
US5047519A (en) | 1986-07-02 | 1991-09-10 | E. I. Du Pont De Nemours And Company | Alkynylamino-nucleotides |
US4810636A (en) | 1986-12-09 | 1989-03-07 | Miles Inc. | Chromogenic acridinone enzyme substrates |
US4774339A (en) | 1987-08-10 | 1988-09-27 | Molecular Probes, Inc. | Chemically reactive dipyrrometheneboron difluoride dyes |
US4945171A (en) | 1987-08-10 | 1990-07-31 | Molecular Probes, Inc. | Xanthene dyes having a fused (C) benzo ring |
US4849362A (en) * | 1988-05-19 | 1989-07-18 | Smithkline Beckman Corporation | Fluorescent intracellular calcium indicators |
US5196306A (en) | 1989-03-29 | 1993-03-23 | E. I. Du Pont De Nemours And Company | Method for the detection or quantitation of an analyte using an analyte dependent enzyme activation system |
US4981977A (en) | 1989-06-09 | 1991-01-01 | Carnegie-Mellon University | Intermediate for and fluorescent cyanine dyes containing carboxylic acid groups |
US5279954A (en) * | 1989-06-30 | 1994-01-18 | Board Of Regents Of The University Of Nebraska And Bionebraska | Exopeptidase catalyzed site-specific bonding of supports, labels and bioactive agents to proteins |
US5132432A (en) | 1989-09-22 | 1992-07-21 | Molecular Probes, Inc. | Chemically reactive pyrenyloxy sulfonic acid dyes |
US5202422A (en) * | 1989-10-27 | 1993-04-13 | The Scripps Research Institute | Compositions containing plant-produced glycopolypeptide multimers, multimeric proteins and method of their use |
US5459276A (en) | 1994-05-20 | 1995-10-17 | Molecular Probes, Inc. | Benzazolylcoumarin-based ion indicators for heavy metals |
US5274113A (en) | 1991-11-01 | 1993-12-28 | Molecular Probes, Inc. | Long wavelength chemically reactive dipyrrometheneboron difluoride dyes and conjugates |
US5433896A (en) | 1994-05-20 | 1995-07-18 | Molecular Probes, Inc. | Dibenzopyrrometheneboron difluoride dyes |
US5227487A (en) | 1990-04-16 | 1993-07-13 | Molecular Probes, Inc. | Certain tricyclic and pentacyclic-hetero nitrogen rhodol dyes |
US5501980A (en) | 1994-05-20 | 1996-03-26 | Molecular Probes, Inc. | Benzazolylcoumarin-based ion indicators |
US5723289A (en) | 1990-06-11 | 1998-03-03 | Nexstar Pharmaceuticals, Inc. | Parallel selex |
US5661016A (en) * | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
DE69127627T2 (de) | 1990-08-29 | 1998-02-19 | Genpharm Int | Produktion und Nützung nicht-menschliche transgentiere zur Produktion heterologe Antikörper |
US5208148A (en) | 1990-12-07 | 1993-05-04 | Molecular Probes, Inc. | Lipophilic fluorescent glycosidase substrates |
US5248782A (en) * | 1990-12-18 | 1993-09-28 | Molecular Probes, Inc. | Long wavelength heteroaryl-substituted dipyrrometheneboron difluoride dyes |
WO1993020096A1 (en) | 1991-05-08 | 1993-10-14 | Stratagene | Oligonucleotide libraries useful for producing primers |
US5451343A (en) | 1991-05-20 | 1995-09-19 | Spectra Group Limited, Inc. | Fluorone and pyronin y derivatives |
US5187288A (en) * | 1991-05-22 | 1993-02-16 | Molecular Probes, Inc. | Ethenyl-substituted dipyrrometheneboron difluoride dyes and their synthesis |
US5637481A (en) | 1993-02-01 | 1997-06-10 | Bristol-Myers Squibb Company | Expression vectors encoding bispecific fusion proteins and methods of producing biologically active bispecific fusion proteins in a mammalian cell |
US5576424A (en) | 1991-08-23 | 1996-11-19 | Molecular Probes, Inc. | Haloalkyl derivatives of reporter molecules used to analyze metabolic activity in cells |
US5242805A (en) | 1991-08-23 | 1993-09-07 | Molecular Probes, Inc. | Long wavelength lipophilic fluorogenic glycosidase substrates |
DE69229174T2 (de) | 1991-08-23 | 1999-09-16 | Molecular Probes, Inc. | Verwendung von haloalkylderivaten von reportermolekülen zur analyse der metabolischen aktivität in zellen |
US5316906A (en) | 1991-08-23 | 1994-05-31 | Molecular Probes, Inc. | Enzymatic analysis using substrates that yield fluorescent precipitates |
CA2141600A1 (en) * | 1992-08-03 | 1994-02-17 | Richard U. Margolis | Cloning, expression and uses for neurocan as a chondroitin sulfate proteoglycan |
AU670108B2 (en) | 1992-09-11 | 1996-07-04 | Becton Dickinson & Company | Improved antibodies to plasmodium falciparum |
US5274133A (en) * | 1993-01-21 | 1993-12-28 | International Flavors & Fragrances Inc. | p-Methylenedioxyphenyl propionitrile derivatives, process for producing same, intermediates used in said process and organoleptic uses of said derivatives and intermediates |
US5808044A (en) | 1993-01-22 | 1998-09-15 | Pharmacia Biotech Inc. | Indocarbocyanine and benzindocarbocyanine phosphoramidites |
US6482919B2 (en) | 1993-02-01 | 2002-11-19 | Bristol-Myers Squibb Company | Expression vectors encoding bispecific fusion proteins and methods of producing biologically active bispecific fusion proteins in a mammalian cell |
US5767259A (en) | 1994-12-27 | 1998-06-16 | Naxcor | Oligonucleotides containing base-free linking groups with photoactivatable side chains |
JP3240866B2 (ja) * | 1995-01-19 | 2001-12-25 | 豊田工機株式会社 | 動力舵取装置 |
SE9500342D0 (sv) * | 1995-01-31 | 1995-01-31 | Marek Kwiatkowski | Novel chain terminators, the use thereof for nucleic acid sequencing and synthesis and a method of their preparation |
US6127134A (en) * | 1995-04-20 | 2000-10-03 | Carnegie Mellon University | Difference gel electrophoresis using matched multiple dyes |
US5843650A (en) | 1995-05-01 | 1998-12-01 | Segev; David | Nucleic acid detection and amplification by chemical linkage of oligonucleotides |
US5798276A (en) | 1995-06-07 | 1998-08-25 | Molecular Probes, Inc. | Reactive derivatives of sulforhodamine 101 with enhanced hydrolytic stability |
US6008373A (en) | 1995-06-07 | 1999-12-28 | Carnegie Mellon University | Fluorescent labeling complexes with large stokes shift formed by coupling together cyanine and other fluorochromes capable of resonance energy transfer |
US5874532A (en) | 1997-01-08 | 1999-02-23 | Nexstar Pharmaceuticals, Inc. | Method for solution phase synthesis of oligonucleotides and peptides |
US6004536A (en) | 1995-11-14 | 1999-12-21 | Molecular Probes, Inc. | Lipophilic cyanine dyes with enchanced aqueous solubilty |
US6162931A (en) | 1996-04-12 | 2000-12-19 | Molecular Probes, Inc. | Fluorinated xanthene derivatives |
DE69706417T2 (de) | 1996-04-19 | 2002-06-27 | Amersham Pharmacia Biotech Uk Ltd., Little Chalfont | Quadratfarbstoffe und deren verwendung in einem fluorescenzsequenzierungsverfahren |
FR2751430B1 (fr) * | 1996-07-16 | 1998-09-11 | Aerospatiale | Dispositif de suspension et de guidage en translation pour un appareil et appareil equipe d'un tel dispositif |
US5846737A (en) | 1996-07-26 | 1998-12-08 | Molecular Probes, Inc. | Conjugates of sulforhodamine fluorophores with enhanced fluorescence |
US5830912A (en) | 1996-11-15 | 1998-11-03 | Molecular Probes, Inc. | Derivatives of 6,8-difluoro-7-hydroxycoumarin |
US5696157A (en) | 1996-11-15 | 1997-12-09 | Molecular Probes, Inc. | Sulfonated derivatives of 7-aminocoumarin |
CA2277159A1 (en) | 1997-01-08 | 1998-07-16 | Wolfgang Pieken | Bioconjugation of macromolecules |
US5948386A (en) * | 1997-03-14 | 1999-09-07 | The Curators Of The University Of Missouri | Conjugate and method for forming aminomethyl phosphorus conjugates |
US5877310A (en) | 1997-04-25 | 1999-03-02 | Carnegie Mellon University | Glycoconjugated fluorescent labeling reagents |
US5773236A (en) | 1997-04-25 | 1998-06-30 | Molecule Probes, Inc. | Assay for glutathiane transferase using polyhaloaryl-substituted reporter molecules |
US6075134A (en) | 1997-05-15 | 2000-06-13 | The Regents Of The University Of California | Glycoconjugates and methods |
EP1009759B1 (en) | 1997-09-05 | 2008-05-28 | Altus Pharmaceuticals Inc. | Carbohydrate crosslinked glycoprotein crystals |
US6130101A (en) | 1997-09-23 | 2000-10-10 | Molecular Probes, Inc. | Sulfonated xanthene derivatives |
US6861254B1 (en) * | 1997-10-24 | 2005-03-01 | Massachusetts Institute Of Technology | Heparan sulfate D-glucosaminyl 3-O-sulfotransferases, and uses therefor |
US6133445A (en) | 1997-12-17 | 2000-10-17 | Carnegie Mellon University | Rigidized trimethine cyanine dyes |
US7427678B2 (en) | 1998-01-08 | 2008-09-23 | Sigma-Aldrich Co. | Method for immobilizing oligonucleotides employing the cycloaddition bioconjugation method |
EP1078023B1 (en) | 1998-04-08 | 2011-01-05 | Corporation Luminex | Luminescent compounds |
US6002003A (en) | 1998-04-14 | 1999-12-14 | Beckman Instruments, Inc. | Cyanine dye activating group with improved coupling selectivity |
JP3983404B2 (ja) | 1999-01-13 | 2007-09-26 | 本田技研工業株式会社 | レーダ搭載車両用ゲート |
US6664047B1 (en) | 1999-04-30 | 2003-12-16 | Molecular Probes, Inc. | Aza-benzazolium containing cyanine dyes |
DE69922498T2 (de) | 1999-07-02 | 2005-12-08 | Visen Medical, Inc., Woburn | Fluorescierende Cyaninlabels mit einem Sulphamidobrückenglied |
EP1219626B1 (en) | 1999-09-20 | 2005-06-01 | Fuji Photo Film Co., Ltd. | Compounds for fluorescence labeling |
AU2001281463A1 (en) * | 2000-03-16 | 2001-09-24 | The Regents Of The University Of California | Chemoselective ligation |
CA2417816A1 (en) * | 2000-08-04 | 2002-02-14 | Molecular Probes, Inc. | Derivatives of 1,2-dihydro-7-hydroxyquinolines containing fused rings |
CA2423806C (en) * | 2000-09-29 | 2009-12-22 | Molecular Probes, Inc. | Modified carbocyanine dyes and their conjugates |
EP3034627B1 (en) | 2000-10-06 | 2019-01-30 | The Trustees of Columbia University in the City of New York | Massive parallel method for decoding dna and rna |
CN2445326Y (zh) * | 2000-10-09 | 2001-08-29 | 刘永详 | 测定被糖化蛋白的免疫分析装置 |
EP1423510A4 (en) * | 2001-08-03 | 2005-06-01 | Glycart Biotechnology Ag | ANTIBODY GLYCOSYLATION VARIANTS WITH INCREASED CELL CYTOTOXICITY DEPENDENT OF ANTIBODIES |
US6406926B1 (en) | 2001-08-15 | 2002-06-18 | Motorola, Inc. | Method of forming a vacuum micro-electronic device |
FI20011671A (fi) | 2001-08-20 | 2003-02-21 | Carbion Oy | Tuumorispesifiset oligosakkaridisekvenssit ja niiden käyttö |
US7214660B2 (en) * | 2001-10-10 | 2007-05-08 | Neose Technologies, Inc. | Erythropoietin: remodeling and glycoconjugation of erythropoietin |
SG159381A1 (en) † | 2001-10-10 | 2010-03-30 | Novo Nordisk As | Remodeling and glycoconjugation of peptides |
US7265085B2 (en) * | 2001-10-10 | 2007-09-04 | Neose Technologies, Inc. | Glycoconjugation methods and proteins/peptides produced by the methods |
US8323903B2 (en) | 2001-10-12 | 2012-12-04 | Life Technologies Corporation | Antibody complexes and methods for immunolabeling |
WO2003046150A2 (en) | 2001-11-28 | 2003-06-05 | Neose Technologies, Inc. | Glycoprotein remodeling using endoglycanases |
US20060205041A1 (en) * | 2001-12-14 | 2006-09-14 | Frye Christopher C | Recombinant bovine thrombin |
JP2005521401A (ja) * | 2002-03-27 | 2005-07-21 | イミュネックス・コーポレーション | ポリペプチド産生を増加させる方法 |
WO2003101972A1 (en) | 2002-05-30 | 2003-12-11 | The Scripps Research Institute | Copper-catalysed ligation of azides and acetylenes |
CN1675245B (zh) * | 2002-06-14 | 2011-01-12 | 免疫医疗公司 | 人源化单克隆抗体hPAM4 |
EP1530578B1 (en) | 2002-08-23 | 2013-03-13 | Illumina Cambridge Limited | Modified nucleotides for polynucleotide sequencing |
US7052843B2 (en) * | 2002-10-08 | 2006-05-30 | New York University | Transcription-based assay for identification of post-translational modification and its application in proteomics |
US20050032081A1 (en) * | 2002-12-13 | 2005-02-10 | Jingyue Ju | Biomolecular coupling methods using 1,3-dipolar cycloaddition chemistry |
AU2004204463B2 (en) | 2003-01-10 | 2009-02-12 | Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services National Institutes Of Health | Catalytic domains of beta(1,4)-galactosyltransferase I having altered donor and acceptor specificities, domains that promote in vitro protein folding, and methods for their use |
WO2005042504A1 (en) | 2003-10-31 | 2005-05-12 | Molecular Probes, Inc. | Fluorinated resorufin compounds and their application in detecting hydrogen peroxide |
ME01775B (me) * | 2003-11-05 | 2011-02-28 | Glycart Biotechnology Ag | Cd20 antitijela sa povećanim afinitetom vezivanja za fc receptor i efektornom funkcijom |
JP2007515625A (ja) | 2003-11-14 | 2007-06-14 | アイアールエム エルエルシー | 生物由来サンプルの選択的処理のためのフルオラス標識化 |
US7070941B2 (en) * | 2003-11-17 | 2006-07-04 | Board Of Regents, The University Of Texas System | Methods and compositions for tagging via azido substrates |
US7332355B2 (en) * | 2003-11-18 | 2008-02-19 | California Institute Of Technology | Method and compositions for the detection of protein glycosylation |
US20070258986A1 (en) † | 2003-11-19 | 2007-11-08 | Govt of the US as represented by the secretary, | Targeted Delivery System for Bioactive Agents |
DE602004015989D1 (de) | 2004-02-10 | 2008-10-02 | Korea Basic Science Inst | Methode zur analyse phosphorylierter stellen und selektives markierungsmittel |
EP2436778A3 (en) | 2004-03-03 | 2012-07-11 | The Trustees of Columbia University in the City of New York | Photocleavable fluorescent nucleotides for DNA sequencing on chip constructed by site-specific coupling chemistry |
JP4601060B2 (ja) | 2004-03-30 | 2010-12-22 | ヤマサ醤油株式会社 | アジド化アミノ糖ヌクレオチド及びその応用 |
WO2006035057A1 (en) | 2004-09-29 | 2006-04-06 | Novo Nordisk Health Care Ag | Modified proteins |
EP1809339A2 (en) | 2004-10-07 | 2007-07-25 | Koninklijke Philips Electronics N.V. | Compounds, kits and methods for use in medical imaging |
US20060147963A1 (en) | 2004-12-30 | 2006-07-06 | Affymetrix, Inc. | Detection of polynucleotides on nucleic acid arrays using azido-modified triphosphate nucleotide analogs |
TWI406952B (zh) | 2005-05-02 | 2013-09-01 | Basf Ag | 分析物之敏感偵測的新標記策略 |
WO2007050811A2 (en) * | 2005-10-27 | 2007-05-03 | The President And Fellows Of Harvard College | Methods and compositions for labeling nucleic acids |
US8114636B2 (en) * | 2006-02-10 | 2012-02-14 | Life Technologies Corporation | Labeling and detection of nucleic acids |
DK1991273T4 (da) * | 2006-02-10 | 2022-02-07 | Life Technologies Corp | Mærkning og påvisning af post-translationelt modificerede proteiner |
IT1395574B1 (it) | 2009-09-14 | 2012-10-16 | Guala Dispensing Spa | Dispositivo di erogazione |
NO3134520T3 (ja) | 2015-04-23 | 2018-05-19 | ||
KR20210157943A (ko) | 2020-06-22 | 2021-12-30 | 현대자동차주식회사 | 자율주행 차량용 통합조작장치 |
US11820402B2 (en) | 2020-07-02 | 2023-11-21 | Qualcomm Incorporated | Motion sickness detection system for autonomous vehicles |
-
2007
- 2007-02-12 DK DK07825657.5T patent/DK1991273T4/da active
- 2007-02-12 EP EP13162088.2A patent/EP2623986B1/en active Active
- 2007-02-12 US US11/674,136 patent/US8716033B2/en active Active
- 2007-02-12 WO PCT/IB2007/003472 patent/WO2008029281A2/en active Application Filing
- 2007-02-12 US US11/674,140 patent/US20070249014A1/en not_active Abandoned
- 2007-02-12 EP EP07756886.3A patent/EP1987068B1/en active Active
- 2007-02-12 EP EP18187681.4A patent/EP3438131B1/en active Active
- 2007-02-12 DK DK07756886.3T patent/DK1987068T3/en active
- 2007-02-12 EP EP07825657.5A patent/EP1991273B2/en active Active
- 2007-02-12 EP EP13162096.5A patent/EP2623609B1/en active Active
- 2007-02-12 WO PCT/US2007/062006 patent/WO2007095506A1/en active Application Filing
- 2007-02-12 JP JP2008553858A patent/JP2009528988A/ja active Pending
- 2007-02-12 DK DK18187681.4T patent/DK3438131T3/da active
- 2007-02-12 EP EP20130162103 patent/EP2623610B1/en not_active Not-in-force
- 2007-02-12 EP EP22156335.6A patent/EP4092418A1/en active Pending
-
2011
- 2011-01-14 US US13/007,506 patent/US8785212B2/en active Active
-
2012
- 2012-02-17 US US13/399,850 patent/US20120301894A1/en not_active Abandoned
-
2014
- 2014-03-21 US US14/221,798 patent/US20140206848A1/en not_active Abandoned
- 2014-06-09 US US14/299,284 patent/US20140377837A1/en not_active Abandoned
- 2014-07-14 US US14/330,727 patent/US9645140B2/en active Active
- 2014-10-10 JP JP2014209061A patent/JP2015044828A/ja not_active Withdrawn
-
2016
- 2016-06-30 JP JP2016129992A patent/JP6646537B2/ja active Active
- 2016-12-20 US US15/385,340 patent/US10676771B2/en active Active
-
2017
- 2017-03-30 US US15/474,901 patent/US20170362624A1/en not_active Abandoned
-
2018
- 2018-06-28 JP JP2018122653A patent/JP2018158943A/ja active Pending
-
2020
- 2020-01-09 US US16/738,274 patent/US20200216871A1/en not_active Abandoned
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6646537B2 (ja) | オリゴ糖によるタンパク質の修飾及び標識方法 | |
US8323903B2 (en) | Antibody complexes and methods for immunolabeling | |
JP2013056934A (ja) | オリゴ糖によるタンパク質の修飾及び標識方法 | |
JP2013056934A6 (ja) | オリゴ糖によるタンパク質の修飾及び標識方法 | |
JP2009531289A6 (ja) | オリゴ糖によるタンパク質の修飾及び標識方法 | |
US8535894B2 (en) | Antibody complexes and methods for immunolabeling | |
AU2002332013A1 (en) | Antibody complexes and methods for immunolabeling |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160729 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20160729 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20161019 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20170517 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20170720 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20171110 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20180228 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20191118 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200110 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6646537 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |