A potent anti-thrombosis peptide (vasotab TY) from horsefly salivary glands

Int J Biochem Cell Biol. 2014 Sep:54:83-8. doi: 10.1016/j.biocel.2014.07.004. Epub 2014 Jul 12.

Abstract

Vasotab TY is a KGD (Lys-Gly-Asp)-containing peptide identified from salivary glands of the horsefly of Tabanus yao. We have previously reported that vasotab TY showed a strong vasodilator activity. In the present study, vasotab TY was found to inhibit platelet aggregation effectively. It completely inhibited platelet aggregation induced by adenosine diphosphate (ADP) at the concentration of 9.6μg/ml. Vasotab TY significantly reduced thrombus weight in rat arteriovenous shunt model and inhibited thrombosis in carrageenan-induced mouse tail thrombosis model in vivo. Vasotab TY competitively bound to glycoprotein IIb/IIIa (GPIIb/IIIa) with eptifibatide, a well-known KGD-containing cyclic heptapeptide containing high specificity and high affinity for GPIIb/IIIa, suggesting that it is an antagonist of the fibrinogen receptor GPIIb/IIIa on the surface of platelet. The KGD motif in vasotab TY may facilitate the binding of it to GPIIb/IIIa. Vasotab TY showed a half-life of more than 1h in vivo. It showed little side effects including little bleeding, no hemolytic activity on human blood red cells and no cytotoxicity on human keratinocyte and THP-1 cells. Combined its vasodilator and platelet inhibitory functions, vasotab TY might be an excellent candidate for the development of clinical anti-thrombosis medicines.

Keywords: Anti-thrombosis; Glycoprotein IIb/IIIa; Horsefly; Platelet inhibitor; Vasodilator.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Diptera / drug effects*
  • Diptera / growth & development
  • Diptera / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • Erythrocytes / drug effects
  • Erythrocytes / metabolism
  • Female
  • Hemolysis / drug effects
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Peptide Fragments / immunology
  • Peptide Fragments / pharmacology*
  • Platelet Aggregation / drug effects*
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
  • Rats
  • Rats, Wistar
  • Salivary Glands / drug effects*
  • Salivary Glands / metabolism
  • Thrombosis / drug therapy*
  • Thrombosis / metabolism

Substances

  • Antibodies, Monoclonal
  • Peptide Fragments
  • Platelet Glycoprotein GPIIb-IIIa Complex