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Isothermal Titration Calorimetry and Inhibition of Platelets Aggregation by D-Phe/(Transcinnamoyl)-Pro-D-Arg-P1'-CONH2 Peptides Inhibitors of Thrombin

机译:D-PhE /(Themcinamoyl)-Pro-D-Arg-P1'-Conh2蛋白质肽抑制剂的血栓抑制剂的等温滴定热量和血小板聚集的抑制作用

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Thrombin is the major product of the plasma coagulation "cascade" of sequential "zymogen-to-protease" steps. As the result of a series of proteolytic cleavages, thrombin converts fibrinogen into fibrin, which deposits at the site of bleeding or thrombosis as the fibrinous portion of a haemostatic plug or thrombotic mass(1). Thrombin also stimulates the platelets through its protein G-coupled receptors PARs (protease activated receptors) (PARI,4 in humans) being their most potent activator. Thrombin induced-platelets activation plays a critical role in the pathophysiology of thrombosis (1). Activated platelets bind to fibrinogen, causing platelets to aggregate at the site of a cardiovascular injury to form a thrombus that is further stabilized by thrombin-generated fibrin network (1). The discovery of new antithrombotic drugs was primarily focused on finding competitive inhibitors of thrombin however new approaches target thrombin receptor PAR-1 (such as the PAR-1 structural antagonists) offering additional cardiovascular utility in the treatment of atherosclerosis and restenosis (1).
机译:凝血酶是顺序“酶原 - 蛋白酶的血浆”等离子体凝固“级联”的主要产物。由于一系列蛋白水解裂解,凝血酶将纤维蛋白原转化为纤维蛋白,其在出血部位或血栓形成的沉积物,作为血压塞或血栓质量的纤维素部分(1)。凝血酶还通过其蛋白质G偶联受体刺激血小板(蛋白酶活化受体)(蛋白酶活化受体)(Pari,4,人体)是它们最有效的活化剂。凝血酶诱导 - 血小板激活在血栓形成的病理生理学中起着关键作用(1)。活化的血小板与纤维蛋白原结合,导致血小板在心血管损伤部位聚集以形成通过凝血酶产生的纤维蛋白网络(1)进一步稳定的血栓。新的抗血栓药物的发现主要集中在凝血酶的竞争性抑制剂中,然而,新方法靶凝血酶受体PAR-1(如PAR-1结构拮抗剂)在治疗动脉粥样硬化和再狭窄(1)中提供额外的心血管效用。

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