30:718:409 Lecture 29: Antithrombotics_Lecture-2_ClassNotes

• School: Rutgers University
• Department: Pharmacology and Toxicology
• Course: 30:718:409
• Professor: Dr. Lavoie and Dr. Chakalamanil

Document Summary

Moa: the dtis bind and inactivate both free thrombin and thrombin bound to fibrin, differences between dtis and heparins. Dtis inhibit only the activity of thrombin: there are three different domains where dtis bind and block the action of thrombin: the active site (or catalytic site, cs) two exosites. Exosite-1 acts as a dock for substrates such as fibrinogen and, thereby, orients the appropriate peptide bonds in the active site for its cleavage. Exosite-2 is the heparin binding domain: bivalent dtis, such as lepirudin and bivalirudin, block thrombin at the active site and exosite-1, whereas univalent dtis argatroban and dabigatran bind only to the active site of the thrombin. Hirudin: hirudin, the lead compound for the design of dtis, is a small protein (65 amino acids) that was originally isolated from the salivary glands of the medicinal leech. Absence of a sulfate group on the tyrosine at position 63.