Isothermal Titration Calorimetry and Inhibition of Platelets Aggregation by [D-Phe/(Transcinnamoyl)-Pro-D-Arg-P1'-CONH2] Peptides Inhibitors of Thrombin
Thrombin is the major product of the plasma coagulation “cascade” of sequential “zymogen-to-protease” steps. As the result of a series of proteolytic cleavages, thrombin converts fibrinogen into fibrin, which deposits at the site of bleeding or thrombosis as the fibrinous portion of a haemostatic plug or thrombotic mass(1). Thrombin also stimulates the platelets through its protein G-coupled receptors PARs (protease activated receptors) (PAR1,4 in humans) being their most potent activator. Thrombin induced-platelets activation plays a critical role in the pathophysiology of thrombosis (1). Activated platelets bind to fibrinogen, causing platelets to aggregate at the site of a cardiovascular injury to form a thrombus that is further stabilized by thrombin-generated fibrin network (1). The discovery of new antithrombotic drugs was primarily focused on finding competitive inhibitors of thrombin, however new approaches target thrombin receptor PAR-1 (such as the PAR-1...
KeywordsPlatelet Aggregation Isothermal Titration Calorimetry Antithrombotic Drug Fibrin Network Peptide Amide
The work was supported by CUNY grants awarded to M. Philipp. We acknowledge the support for conducting ITC experiments in the lab of Professor Richard Magliozzo, Broolyn College, CUNY.