Anticoagulant and antiprotease activities of a heparinoid sulfated glucoside-bearing polymer.
We studied anticoagulant and antiprotease activities of the poly(glucosyloxyethyl methacrylate) sulfate [poly(GEMA)-sulfate] in plasma and purified enzyme systems in order to evaluate the anticoagulant behavior of a heparin-like sulfated glucoside-bearing polymer. As a result, we found that poly(GEMA)-sulfate can inhibit some coagulation proteases, although its antiprotease behavior differed from those of heparin and dextran sulfate. Poly(GEMA)-sulfate could not enhance antithrombin activity; therefore, we did not observe any significant inhibition of Factor Xa via antithrombin. However, we found that poly(GEMA)-sulfate was able to inhibit thrombin through the activation of heparin cofactor II. In addition, poly(GEMA)-sulfate was able to inhibit Tenase. In our previous research. we found that the anticoagulant activity of poly(GEMA)-sulfate is due primarily to the formation of an insoluble complex with fibrinogen. This paper showed that the antiprotease activities of poly(GEMA)-sulfate contribute to some extent to its anticoagulant activity.
Onishi
M
M
R&D Department, Terumo Corp., Kanagawa, Japan.
Miyashita
Y
Y
Motomura
T
T
Yamashita
S
S
Sakamoto
N
N
Akashi
M
M
D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology*; D000990:Antithrombin III / Q000737:chemistry / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects* / Q000502:physiology; D003911:Dextrans / Q000737:chemistry / Q000494:pharmacology; D004151:Dipeptides / Q000737:chemistry; D015951:Factor Xa / Q000737:chemistry / Q000494:pharmacology; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology; D015844:Heparin Cofactor II / Q000737:chemistry / Q000494:pharmacology; D006496:Heparinoids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry; D010314:Partial Thromboplastin Time; D011109:Polymethacrylic Acids / Q000737:chemistry / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D013053:Spectrophotometry
D000925:Anticoagulants; D003911:Dextrans; D004151:Dipeptides; D005960:Glucosides; D006496:Heparinoids; D009842:Oligopeptides; D011109:Polymethacrylic Acids; D011480:Protease Inhibitors; D015842:Serine Proteinase Inhibitors; C103218:poly(glucosyloxyethyl methacrylate) sulfate; C015608:benzoyl-Ile-Glu-Gly-Arg-p-nitroanilide; C021129:S 2238; D015844:Heparin Cofactor II; D000990:Antithrombin III; D006493:Heparin; D015951:Factor Xa