嵌合水蛭肽的构建与活性分析  

Construction and Activity Analysis of Fused Hirudin Peptide

作　　者：沈雳[1] 陈少萍[1] 蔡在龙[2] 杨生生[2] 秦永文[1] 

机构地区：[1]第二军医大学长海医院心内科,上海200433 [2]第二军医大学基础医学部生物化学与分子生物学教研室,上海200433

出　　处：《中国生物化学与分子生物学报》2004年第5期702-706,共5页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金 (No .3 0 2 0 0 2 81)资助~~

摘　　要：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.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.

关 键 词：血栓 水蛭素 抗凝血酶功能 嵌合水蛭肽 

分 类 号：Q[生物学]