Chemical modification of alpha-thrombin and in vitro characterization of its anticoagulant activity.
Acetylthrombin, succinylthrombin, maleylthrombin, polyethylene glycol (PEG)-thrombin, and acetylated PEG-thrombin were prepared and characterized. Although clotting activities could be reduced remarkably by the modification, the potencies of all the modified thrombins for protein C activation also decreased. However, in the case of acetylthrombin, succinylthrombin, and acetylated PEG-thrombin, the remaining potencies for protein C activation exceeded largely the remaining clotting activities. Moreover, by the addition of thrombodulin, the potencies for protein C activation were enhanced 16 - 60 fold for succinylthrombin, maleylthrombin, and PEG-thrombin.
Nakagomi
K
K
Bioorganic Chemistry Division, Meiji Institute of Health Science, Meiji Milk Products Co., Ltd., Odawara, Japan.
Ajisaka
K
K
D000818:Animals; D000925:Anticoagulants; D000990:Antithrombin III / Q000494:pharmacology; D001777:Blood Coagulation; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011486:Protein C / Q000378:metabolism*; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000494:pharmacology; D018179:Receptors, Thrombin; D013917:Thrombin / Q000737:chemistry / Q000378:metabolism*
D000925:Anticoagulants; D010880:Piperidines; D011486:Protein C; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; D010649:Phenylalanine; D000990:Antithrombin III; D005340:Fibrinogen; C054648:N-dansyl-(1,4-guanidino)phenylalanine piperdide; D013917:Thrombin