Mor A, Maillard J, Favreau C, Reboud-Ravaux M
Laboratoire de Bioactivation des Peptides, Institut Jacques Monod, Paris, France.
Biochim Biophys Acta. 1990 Mar 29;1038(1):119-24. doi: 10.1016/0167-4838(90)90019-c.
Thrombin, plasmin and tissue plasminogen activator (one- and two-chain forms) were examined with respect to their reaction with the suicide substrate, 3,4-dihydro-3-benzyl-6-chloromethylcoumarin, at 4 degrees C. The enzymes were irreversibly inhibited and the apparent second-order rate constants ki/Ki were 31,000, 316, 187 and 250 M-1.s-1, respectively. The extent of fibrin clot lysis induced by urokinase and two-chain tissue plasminogen activator was considerably decreased after treatment of these enzymes with the dihydrocoumarin derivative (molar excess of inhibitor over enzyme ranging from 6 to 21 for urokinase and 50 to 1500 for tissue plasminogen activator). This inhibitor has been tested as anticoagulant in human plasma and was effective at prolonging the prothrombin time from 12 to 40 s.
在4℃下，研究了凝血酶、纤溶酶和组织纤溶酶原激活剂（单链和双链形式）与自杀底物3,4-二氢-3-苄基-6-氯甲基香豆素的反应。这些酶被不可逆地抑制，表观二级速率常数ki/Ki分别为31,000、316、187和250 M-1·s-1。用二氢香豆素衍生物处理这些酶后（抑制剂与酶的摩尔过量比，尿激酶为6至21，组织纤溶酶原激活剂为五十至1500），尿激酶和双链组织纤溶酶原激活剂诱导的纤维蛋白凝块溶解程度显著降低。该抑制剂已在人血浆中作为抗凝剂进行测试，可有效将凝血酶原时间从12秒延长至40秒。
