DE69711765T2 - Phrothrombin und Thrombin bindende Peptide. - Google Patents
Phrothrombin und Thrombin bindende Peptide.Info
- Publication number
- DE69711765T2 DE69711765T2 DE69711765T DE69711765T DE69711765T2 DE 69711765 T2 DE69711765 T2 DE 69711765T2 DE 69711765 T DE69711765 T DE 69711765T DE 69711765 T DE69711765 T DE 69711765T DE 69711765 T2 DE69711765 T2 DE 69711765T2
- Authority
- DE
- Germany
- Prior art keywords
- thrombin
- peptide
- seq
- leu
- gly
- 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.)
- Expired - Lifetime
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 82
- 108090000190 Thrombin Proteins 0.000 title claims abstract description 75
- 229960004072 thrombin Drugs 0.000 title claims abstract description 48
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 26
- 230000027455 binding Effects 0.000 title description 19
- 108010094028 Prothrombin Proteins 0.000 claims abstract description 25
- 102100027378 Prothrombin Human genes 0.000 claims abstract description 23
- 229940039716 prothrombin Drugs 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 12
- FKYQEVBRZSFAMJ-QWRGUYRKSA-N Gly-Ser-Tyr Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 FKYQEVBRZSFAMJ-QWRGUYRKSA-N 0.000 claims abstract 4
- 108090000623 proteins and genes Proteins 0.000 claims description 32
- 102000004169 proteins and genes Human genes 0.000 claims description 31
- 239000000758 substrate Substances 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims 1
- 239000003446 ligand Substances 0.000 abstract description 12
- 238000001042 affinity chromatography Methods 0.000 abstract description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 50
- 239000011347 resin Substances 0.000 description 33
- 229920005989 resin Polymers 0.000 description 33
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
- 229940024606 amino acid Drugs 0.000 description 29
- 235000001014 amino acid Nutrition 0.000 description 29
- 150000001413 amino acids Chemical group 0.000 description 28
- 235000018102 proteins Nutrition 0.000 description 28
- 239000011780 sodium chloride Substances 0.000 description 25
- 239000006167 equilibration buffer Substances 0.000 description 13
- 238000010828 elution Methods 0.000 description 10
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 9
- QWXZOFZKSQXPDC-NSHDSACASA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)propanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](C)C(O)=O)C3=CC=CC=C3C2=C1 QWXZOFZKSQXPDC-NSHDSACASA-N 0.000 description 8
- 238000013375 chromatographic separation Methods 0.000 description 7
- 239000000499 gel Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 239000001509 sodium citrate Substances 0.000 description 6
- 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 6
- 238000001262 western blot Methods 0.000 description 6
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 5
- 238000002835 absorbance Methods 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000011324 bead Substances 0.000 description 5
- 231100000673 dose–response relationship Toxicity 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 4
- 239000007995 HEPES buffer Substances 0.000 description 4
- 238000010306 acid treatment Methods 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 239000001110 calcium chloride Substances 0.000 description 4
- 235000011148 calcium chloride Nutrition 0.000 description 4
- 229910001628 calcium chloride Inorganic materials 0.000 description 4
- 238000005277 cation exchange chromatography Methods 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 230000010354 integration Effects 0.000 description 4
- 239000011534 wash buffer Substances 0.000 description 4
- 241000272194 Ciconiiformes Species 0.000 description 3
- 108010049003 Fibrinogen Proteins 0.000 description 3
- 102000008946 Fibrinogen Human genes 0.000 description 3
- 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 3
- -1 L-arginyl methyl Chemical group 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- 101800004937 Protein C Proteins 0.000 description 3
- 102000017975 Protein C Human genes 0.000 description 3
- 101800001700 Saposin-D Proteins 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000003599 detergent Substances 0.000 description 3
- 239000012149 elution buffer Substances 0.000 description 3
- 229960002897 heparin Drugs 0.000 description 3
- 229920000669 heparin Polymers 0.000 description 3
- 239000012145 high-salt buffer Substances 0.000 description 3
- 229920002401 polyacrylamide Polymers 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 229960000856 protein c Drugs 0.000 description 3
- 238000004007 reversed phase HPLC Methods 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- QEIFSLUFHRCVQL-UHFFFAOYSA-N (5-bromo-4-chloro-1h-indol-3-yl) hydrogen phosphate;(4-methylphenyl)azanium Chemical compound CC1=CC=C(N)C=C1.C1=C(Br)C(Cl)=C2C(OP(O)(=O)O)=CNC2=C1 QEIFSLUFHRCVQL-UHFFFAOYSA-N 0.000 description 2
- 108010043797 4-alpha-glucanotransferase Proteins 0.000 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 102100040894 Amylo-alpha-1,6-glucosidase Human genes 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 108010062466 Enzyme Precursors Proteins 0.000 description 2
- 102000010911 Enzyme Precursors Human genes 0.000 description 2
- 108010073385 Fibrin Proteins 0.000 description 2
- 102000009123 Fibrin Human genes 0.000 description 2
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 2
- 102000007625 Hirudins Human genes 0.000 description 2
- 108010007267 Hirudins Proteins 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 108010067902 Peptide Library Proteins 0.000 description 2
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 229940096437 Protein S Drugs 0.000 description 2
- 108010066124 Protein S Proteins 0.000 description 2
- 102000029301 Protein S Human genes 0.000 description 2
- 244000061456 Solanum tuberosum Species 0.000 description 2
- 235000002595 Solanum tuberosum Nutrition 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 229930003448 Vitamin K Natural products 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 238000001261 affinity purification Methods 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000013522 chelant Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000012539 chromatography resin Substances 0.000 description 2
- 238000005345 coagulation Methods 0.000 description 2
- 230000015271 coagulation Effects 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
- 229950003499 fibrin Drugs 0.000 description 2
- 229940012952 fibrinogen Drugs 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 229940006607 hirudin Drugs 0.000 description 2
- WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 description 2
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
- 230000000415 inactivating effect Effects 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 150000003354 serine derivatives Chemical class 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 229960003766 thrombin (human) Drugs 0.000 description 2
- 235000019168 vitamin K Nutrition 0.000 description 2
- 239000011712 vitamin K Substances 0.000 description 2
- 150000003721 vitamin K derivatives Chemical class 0.000 description 2
- 229940046010 vitamin k Drugs 0.000 description 2
- JCEZOHLWDIONSP-UHFFFAOYSA-N 3-[2-[2-(3-aminopropoxy)ethoxy]ethoxy]propan-1-amine Chemical group NCCCOCCOCCOCCCN JCEZOHLWDIONSP-UHFFFAOYSA-N 0.000 description 1
- CXNVOWPRHWWCQR-UHFFFAOYSA-N 4-Chloro-ortho-toluidine Chemical compound CC1=CC(Cl)=CC=C1N CXNVOWPRHWWCQR-UHFFFAOYSA-N 0.000 description 1
- WPANETAWYGDRLL-UHFFFAOYSA-N 4-aminobenzenecarboximidamide Chemical compound NC(=N)C1=CC=C(N)C=C1 WPANETAWYGDRLL-UHFFFAOYSA-N 0.000 description 1
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 108010008184 Aryldialkylphosphatase Proteins 0.000 description 1
- 102000006996 Aryldialkylphosphatase Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 241000255945 Choristoneura Species 0.000 description 1
- 108010044316 Cohn fraction III Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
- 101710096438 DNA-binding protein Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 108010074860 Factor Xa Proteins 0.000 description 1
- 108010080379 Fibrin Tissue Adhesive Proteins 0.000 description 1
- 241000204946 Halobacterium salinarum Species 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 241000598171 Human adenovirus sp. Species 0.000 description 1
- QNAYBMKLOCPYGJ-UWTATZPHSA-N L-Alanine Natural products C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 241000222727 Leishmania donovani Species 0.000 description 1
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 241000829388 Mus musculus polyomavirus 1 Species 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 101710185500 Small t antigen Proteins 0.000 description 1
- 240000006394 Sorghum bicolor Species 0.000 description 1
- 235000007230 Sorghum bicolor Nutrition 0.000 description 1
- 108010039811 Starch synthase Proteins 0.000 description 1
- 102000019197 Superoxide Dismutase Human genes 0.000 description 1
- 108010012715 Superoxide dismutase Proteins 0.000 description 1
- 102000006943 Uracil-DNA Glycosidase Human genes 0.000 description 1
- 108010072685 Uracil-DNA Glycosidase Proteins 0.000 description 1
- QWXOJIDBSHLIFI-UHFFFAOYSA-N [3-(1-chloro-3'-methoxyspiro[adamantane-4,4'-dioxetane]-3'-yl)phenyl] dihydrogen phosphate Chemical compound O1OC2(C3CC4CC2CC(Cl)(C4)C3)C1(OC)C1=CC=CC(OP(O)(O)=O)=C1 QWXOJIDBSHLIFI-UHFFFAOYSA-N 0.000 description 1
- 229960003767 alanine Drugs 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- WLDHEUZGFKACJH-UHFFFAOYSA-K amaranth Chemical compound [Na+].[Na+].[Na+].C12=CC=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(O)=C1N=NC1=CC=C(S([O-])(=O)=O)C2=CC=CC=C12 WLDHEUZGFKACJH-UHFFFAOYSA-K 0.000 description 1
- 239000003957 anion exchange resin Substances 0.000 description 1
- 239000002506 anticoagulant protein Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000000356 contaminant Substances 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
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 238000013500 data storage Methods 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 230000002439 hemostatic effect Effects 0.000 description 1
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
- 229940127121 immunoconjugate Drugs 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 230000036457 multidrug resistance Effects 0.000 description 1
- ANORDWOIBSUYBN-UHFFFAOYSA-N n-chloro-1-phenylmethanamine Chemical compound ClNCC1=CC=CC=C1 ANORDWOIBSUYBN-UHFFFAOYSA-N 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 229940024790 prothrombin complex concentrate Drugs 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000001044 red dye Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000000565 sealant Substances 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000003001 serine protease inhibitor Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000012622 synthetic inhibitor Substances 0.000 description 1
- 108010031354 thermitase Proteins 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- 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
- C07K14/745—Blood coagulation or fibrinolysis factors
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6429—Thrombin (3.4.21.5)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21005—Thrombin (3.4.21.5)
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Hematology (AREA)
- Microbiology (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Enzymes And Modification Thereof (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/672,805 US5831003A (en) | 1996-06-28 | 1996-06-28 | Peptides which bind to prothrombin and thrombin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69711765D1 DE69711765D1 (de) | 2002-05-16 |
| DE69711765T2 true DE69711765T2 (de) | 2002-10-02 |
Family
ID=24700072
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69711765T Expired - Lifetime DE69711765T2 (de) | 1996-06-28 | 1997-06-16 | Phrothrombin und Thrombin bindende Peptide. |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US5831003A (enExample) |
| EP (1) | EP0816377B1 (enExample) |
| JP (1) | JP3978258B2 (enExample) |
| AT (1) | ATE215964T1 (enExample) |
| AU (1) | AU712575B2 (enExample) |
| CA (1) | CA2206663A1 (enExample) |
| DE (1) | DE69711765T2 (enExample) |
| DK (1) | DK0816377T3 (enExample) |
| ES (1) | ES2175218T3 (enExample) |
| PT (1) | PT816377E (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6462180B1 (en) * | 1999-11-24 | 2002-10-08 | Bayer Corporation | Method of preparing α-1 proteinase inhibitor |
| EP1343809B2 (en) | 2000-12-14 | 2023-03-15 | Grifols Therapeutics Inc. | Method of preparing alpha-1 proteinase inhibitor |
| GB0211849D0 (en) * | 2002-05-23 | 2002-07-03 | Mok Kenneth H | Improvments to retro-inverso isomers |
| FR2884418B1 (fr) * | 2005-04-15 | 2008-11-21 | Soc Extraction Principes Actif | Utilisation d'un peptide comme principe actif amincissant |
| EP2502628B1 (en) | 2006-06-23 | 2016-12-14 | Alethia Biotherapeutics Inc. | Polynucleotides and polypeptide sequences involved in cancer |
| WO2010060186A1 (en) | 2008-11-03 | 2010-06-03 | Alethia Biotherapeutics Inc. | Antibodies that specifically block the biological activity of a tumor antigen |
| US8945895B2 (en) | 2009-07-31 | 2015-02-03 | Baxter International Inc. | Methods of purifying recombinant ADAMTS13 and other proteins and compositions thereof |
| DK3173427T3 (da) | 2011-03-31 | 2019-08-05 | Adc Therapeutics Sa | Antistoffer mod nyre-associeret antigen 1 og antigen-bindende fragmenter deraf |
| HRP20190946T1 (hr) | 2012-01-09 | 2019-07-26 | Adc Therapeutics Sa | Sredstva za liječenje trostruko negativnog raka dojke |
| EP3262409B1 (en) | 2015-02-25 | 2020-03-25 | Omrix Biopharmaceuticals Ltd. | Method for purifying and quantifying thrombin and its degradation polypeptides |
| ES2791982T3 (es) * | 2015-02-25 | 2020-11-06 | Omrix Biopharmaceuticals Ltd | Método para purificar y cuantificar la trombina y sus polipéptidos de degradación |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1341032C (en) * | 1987-01-23 | 2000-06-20 | John L. Krstenansky | Anticoagulant peptides |
| US5367060A (en) * | 1991-05-24 | 1994-11-22 | Genentech, Inc. | Structure, production and use of heregulin |
-
1996
- 1996-06-28 US US08/672,805 patent/US5831003A/en not_active Expired - Lifetime
-
1997
- 1997-06-16 ES ES97109744T patent/ES2175218T3/es not_active Expired - Lifetime
- 1997-06-16 AT AT97109744T patent/ATE215964T1/de active
- 1997-06-16 DE DE69711765T patent/DE69711765T2/de not_active Expired - Lifetime
- 1997-06-16 DK DK97109744T patent/DK0816377T3/da active
- 1997-06-16 PT PT97109744T patent/PT816377E/pt unknown
- 1997-06-16 EP EP97109744A patent/EP0816377B1/en not_active Expired - Lifetime
- 1997-06-23 AU AU26220/97A patent/AU712575B2/en not_active Ceased
- 1997-06-24 JP JP18189597A patent/JP3978258B2/ja not_active Expired - Fee Related
- 1997-06-25 CA CA002206663A patent/CA2206663A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CA2206663A1 (en) | 1997-12-28 |
| PT816377E (pt) | 2002-08-30 |
| DK0816377T3 (da) | 2002-07-22 |
| AU712575B2 (en) | 1999-11-11 |
| DE69711765D1 (de) | 2002-05-16 |
| JP3978258B2 (ja) | 2007-09-19 |
| EP0816377B1 (en) | 2002-04-10 |
| EP0816377A2 (en) | 1998-01-07 |
| EP0816377A3 (en) | 1998-07-15 |
| AU2622097A (en) | 1998-01-15 |
| ATE215964T1 (de) | 2002-04-15 |
| US5831003A (en) | 1998-11-03 |
| JPH1075778A (ja) | 1998-03-24 |
| ES2175218T3 (es) | 2002-11-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Holt et al. | Characterization of human platelet basic protein, a precursor form of low-affinity platelet factor 4 and. beta.-thromboglobulin | |
| DE68915675T3 (de) | Verfahren zur Reinigung von Vitamin K-abhängigen Proteinen. | |
| Boissel et al. | Covalent structures of beta and gamma autolytic derivatives of human alpha-thrombin. | |
| Ambler | The amino acid sequence of Staphylococcus aureus penicillinase | |
| Vahlquist et al. | Isolation of the human retinol binding protein by affinity chromatography | |
| KR101293504B1 (ko) | 혼합형 또는 다중형 수지를 사용하는 인자 ｖⅰⅰⅰ의 정제 | |
| US4749780A (en) | Biologically active fragments of human antihemophilic factor and method for preparation thereof | |
| DE69711765T2 (de) | Phrothrombin und Thrombin bindende Peptide. | |
| CA2315309A1 (en) | Process for the preparation in pure form of the protease activating blood clotting factor vii, its proenzyme or a mixture of both proteins by means of affinity chromatography | |
| US6677440B1 (en) | Process for the preparation in pure form of the protease activating blood clotting factor VII, its proenzyme or a mixture of both proteins by means of ion-exchange chromatography | |
| EP1012191B1 (de) | VERFAHREN ZUR GEWINNUNG VON HOCHREINEM vWF ODER FACTOR VIII/vWF-KOMPLEX | |
| JPH08119997A (ja) | フォンウィルブランド因子の高分子および低分子フラクション | |
| Baglia et al. | Localization of the high molecular weight kininogen binding site in the heavy chain of human factor XI to amino acids phenylalanine 56 through serine 86. | |
| Pierce et al. | Further characterization of highly purified human plasma kininogens | |
| Nakayama et al. | Use of a monoclonal antibody to purify the tetrodotoxin binding component from the electroplax of Electrophorus electricus. | |
| DePoli et al. | Thrombospondin interaction with plasminogen. Evidence for binding to a specific region of the kringle structure of plasminogen | |
| US6034222A (en) | Method for the separation of recombinant pro-factor IX from recombinant factor IX | |
| DE60003449T2 (de) | Testverfahren | |
| Velander et al. | Process implications for metal‐dependent immunoaffinity interactions | |
| Pierce | Purification of mammalian kallikreins, kininogens, and kinins | |
| US5998589A (en) | Method of purifying human factor VIII | |
| AU757858B2 (en) | Process for the separation of glycosylated and non-glycosylated proteins | |
| WO2000031121A1 (en) | Recombinant factor viii binding peptides | |
| Herion et al. | Purification of urokinase by monoclonal antibody affinity chromatography | |
| Benarous et al. | Human prothrombin: a new method of preparation from a single individual |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |