嵌合水蛭肽的构建与活性分析

血管成形术或动脉粥样斑块破裂等因素所致血管壁损伤而引起的血栓形成过程中 ,血小板的激活和凝血酶的形成起着关键作用 .因此 ,抗血小板和抗凝是治疗血栓的两个重要方面 .血小板膜糖蛋白GPⅡb Ⅲa受体拮抗剂 ,如含Arg Gly Asp(RGD)序列的多肽 ,在临床上已显示了良好的抗血小板

Construction and Activity Analysis of Fused Hirudin Peptide

A fused hirudin peptide was designed, synthesized and purified and its antithrombin and antiplatelet functions were tested.This bifunctional anticoagulation peptide was composed of three inhibitory regions: (1)the tail of hirudin (hirudin 53-64 ), a potent direct antithrombin , binds to the anion binding exosite (ABE) of thrombin.Hirudin 53-64 blocks fibrinogen recognition site of thrombin and consequently inhibits thrombin directly;(2) Arg -Pro -Pro -Gly - Phe (RPPGF) amino acid sequence, a metabolite of bradykinin,binds to the active site of thrombin and thereby inhibits the amidolytic activity of thrombin;(3)Arg-Gly-Asp(RGD)amino acid sequence, an inhibitor of GP IIb/IIIa, blocks the final path of platelets aggregation by preventing fibrinogen binding to platelets. This 26 amino acid fused hirudin peptide was artificially synthesized, purified and analysed.The study finally showed that the fused hirudin peptide had activities of antithrombin and antiplatelet. It is feasible to construct a hybrid multifunctional peptide that targets various components of haemostatic process.