Enhanced protein C activation and inhibition of fibrinogen cleavage by a thrombin modulator

被引:45
作者
Berg, DT [1 ]
Wiley, MR [1 ]
Grinnell, BW [1 ]
机构
[1] LILLY RES LABS,CARDIOVASC RES DIV,INDIANAPOLIS,IN 46285
关键词
D O I
10.1126/science.273.5280.1389
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1389 / 1391
页数:3
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