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Isothermal Titration Calorimetry and Inhibition of Platelets Aggregation by [D-Phe/(Transcinnamoyl)-Pro-D-Arg-P1'-CONH2] Peptides Inhibitors of Thrombin

  • Cristina C. Clement
  • Anna Babinska
  • Elizabeth Kornecki
  • Manfred Philipp
Part of the Advances in Experimental Medicine and Biology book series (volume 611)

Introduction

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...

Keywords

Platelet Aggregation Isothermal Titration Calorimetry Antithrombotic Drug Fibrin Network Peptide Amide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

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.

References

  1. 1.
    S. Chackalamannil et.al. J. Med. Chem. 48, 5884–5887 (2005).CrossRefGoogle Scholar
  2. 2.
    C.C. Clement and M. Philipp. Proceeding of American Peptide Society, Sylvie E. Blondelle (Editor) July 2005.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Cristina C. Clement
    • 1
  • Anna Babinska
    • 2
  • Elizabeth Kornecki
    • 2
  • Manfred Philipp
    • 1
  1. 1.Department of Chemistry, Lehman CollegeCity University of New YorkBronx, NYUSA
  2. 2.Department of Anatomy and Cell BiologySUNY Downstate Medical CenterBrooklyn, NYUSA

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