Shebuski R J, Berry D E, Bennett D B, Romoff T, Storer B L, Ali F, Samanen J
Department of Pharmacology, Smith Kline & French Laboratories, King of Prussia, PA.
Thromb Haemost. 1989 Apr 25;61(2):183-8.
This study compared the anti-platelet effect of Ac-RGDS-NH2 which is a peptide fragment from fibrinogen to Ac-RGES-NH2 in which the aspartic acid (D) of Ac-RGDS-NH2 has been replaced by glutamic acid (E). When Ac-RGDS-NH2 was infused intracoronary at concentrations of 100-400 mM, acute platelet-dependent thrombus formation in the dog coronary artery was inhibited. However, infusion of Ac-RGES-NH2 intracoronary at similar concentrations to Ac-RGDS-NH2 failed to inhibit platelet-dependent thrombus formation in the dog. Ac-RGDS-NH2 and Ac-RGES-NH2 were also tested for their ability to inhibit collagen-induced platelet aggregation in vitro. Ac-RGDS-NH2 elicited concentration-dependent inhibition of collagen-induced aggregation with no effect of Ac-RGES-NH2 on collagen-induced platelet aggregation. Thus, Ac-RGDS-NH2 is an effective antiplatelet agent after intracoronary administration in the dog and also inhibits collagen-induced platelet aggregation in vitro. Ac-RGDS-NH2 is a specific inhibitor of platelet aggregation as replacement of the aspartic acid in Ac-RGDS-NH2 with glutamic acid results in complete loss of biological activity.
本研究比较了纤维蛋白原的肽片段Ac-RGDS-NH2与Ac-RGES-NH2的抗血小板作用，其中Ac-RGDS-NH2中的天冬氨酸（D）已被谷氨酸（E）取代。当以100 - 400 mM的浓度冠状动脉内注入Ac-RGDS-NH2时，犬冠状动脉内急性血小板依赖性血栓形成受到抑制。然而，以与Ac-RGDS-NH2相似的浓度冠状动脉内注入Ac-RGES-NH2未能抑制犬的血小板依赖性血栓形成。还测试了Ac-RGDS-NH2和Ac-RGES-NH2在体外抑制胶原诱导的血小板聚集的能力。Ac-RGDS-NH2引起胶原诱导聚集的浓度依赖性抑制，而Ac-RGES-NH2对胶原诱导的血小板聚集无影响。因此，Ac-RGDS-NH2在犬冠状动脉内给药后是一种有效的抗血小板药物，并且在体外也抑制胶原诱导的血小板聚集。Ac-RGDS-NH2是血小板聚集的特异性抑制剂，因为用谷氨酸取代Ac-RGDS-NH2中的天冬氨酸会导致生物活性完全丧失。
