Enhanced protein C activation and inhibition of fibrinogen cleavage by a thrombin modulator
Enhanced protein C activation and inhibition of fibrinogen cleavage by a thrombin modulator
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DOI：
10.1126/science.273.5280.1389
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发表时间：
1996-09-06
期刊：
影响因子：
56.9
通讯作者：
Grinnell, BW
中科院分区：
文献类型：
--
作者：
Berg, DT;Wiley, MR;Grinnell, BW
鉴定出一种人凝血酶酶活性调节剂，命名为 LY254603，可增强凝血酶催化的抗凝因子激活蛋白 C 的生成，同时抑制凝血酶依赖性纤维蛋白原凝固。通过突变底物，表明 LY254603 通过改变凝血酶的 S3 底物识别来介导酶底物特异性的变化位点，这种机制似乎与钠离子或血栓调节蛋白诱导的变构变化无关。该化合物可能代表一类专门调节凝血酶促凝血和抗凝血功能之间平衡的药物的原型。
A modulator of the enzymatic activity of human thrombin, designated LY254603, was identified that enhances the thrombin-catalyzed generation of the anticoagulant factor activated protein C, yet inhibits thrombin-dependent fibrinogen clotting, By means of mutant substrates, it was shown that LY254603 mediates the change in enzymatic substrate specificity through an alteration in thrombin's S3 substrate recognition site, a mechanism that appeared to be independent of allosteric changes induced by either sodium ions or by thrombomodulin. This compound may represent the prototype of a class of agents that specifically modulates the balance between thrombin's procoagulant and anticoagulant functions.