Enhanced Protein C Activation and Inhibition of Fibrinogen Cleavage by a Thrombin Modulator
- 6 September 1996
- journal article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 273 (5280) , 1389-1391
- https://doi.org/10.1126/science.273.5280.1389
Abstract
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.Keywords
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