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 tai...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.展开更多
文摘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.
