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

摘要

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 9.6 |xg/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 glycopro-tein 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 1 h in vivo. It showed little side effects including little bleeding, no hemolytic activity on human blood red cells and no cytotoxicity on human keratino-cyte 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.