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Modulation of thrombin's procoagulant and anticoagulant properties THROMBOSIS AND HAEMOSTASIS Leung, L. L., Gibbs, C. S. 1997; 78 (1): 577-580

Abstract

The procoagulant and anticoagulant functions of thrombin are controlled physiologically by allosteric changes induced by Na+ and vascular cell-surface TM. Key residues that mediate Na+ interaction with thrombin have been identified. Based on a site-directed mutagenesis approach, E229K thrombin is found to be the most optimal and potent PC activator with a marked shift in substrate specificity for PC over fibrinogen. E229K thrombin demonstrates significant anticoagulant and antithrombotic efficacy in animal models in vivo. Alternatively, a synthetic organic molecule (LY254603) has been discovered which interacts with thrombin and effectively modulates its functions in vitro. This new class of antithrombotic agents exploits the powerful natural PC anticoagulant pathway and may have a superior therapeutic profile than direct thrombin inhibitors.

View details for Web of Science ID A1997XE83800102

View details for PubMedID 9198219