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  • Title: Enhanced protein C activation and inhibition of fibrinogen cleavage by a thrombin modulator.
    Author: Berg DT, Wiley MR, Grinnell BW.
    Journal: Science; 1996 Sep 06; 273(5280):1389-91. PubMed ID: 8703074.
    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.
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