Analysis of the Potent Platelet Glycoprotein IIb-IIIa Antagonist from Natural Sources

  • Kang, In-Cheol (Department of Biochemistry, College of Science, and Bioproducts Research Center, Yonsei University) ;
  • Kim, Doo-Sik (Department of Biochemistry, College of Science, and Bioproducts Research Center, Yonsei University)
  • Received : 1998.05.18
  • Accepted : 1998.06.05
  • Published : 1998.09.30

Abstract

Adhesive interaction of the platelet glycoprotien IIb-IIIa (GP IIb-IIIa) with a plasma protein, such as fibrinogen, plays an important role in thrombosis and hemostasis. The specific sequence Arg-Gly-Asp (RGD) is critical for the binding of fibrinogen to platelet. To examine and characterize the GP IIb-IIIa antagonist from natural sources, we have developed a simple enzyme-linked immunosorbant assay (ELISA) system. The GP IIb-IIIa complex was purified to homogeneity from platelet Iysates by the combination of two affinity chromatographic methods using the synthetic RGD peptide (GRGDSPK)-immobilized Sepharose and wheat germ lectin-Sepharose. The synthetic peptide GRGDSP inhibits GP IIb-IIIa binding to immobilized fibrinogen with an $IC_{50}$ of $1.5\;{\mu}M$. Venoms of three different snake species and a Korean scolopendra extract have strong antagonistic activities for the binding of human fibrinogen to the platelet GP IIb-IIIa complex. The $IC_{50}$ values of the snake venom s and scolopendra were in the range of $5.5\;{\mu}g$ to $60\;{\mu}g$. These results provide meaningful information for developing antiplatelet agents.

Keywords

GP IIb-IIIa antagionist;Platelet