血小板GPIIb/IIIa受体与纤维蛋白原结合，是血小板聚集的最后通路。GPIIb/IIIa受体拮抗剂是目前最有效的抗血小板聚集药物之一。本课题组研究发现的结构新颖的天然活性多肽AAP是一种GPIIb/IIIa受体拮抗剂，它能够高效抑制PAF、ADP、胶原和凝血酶诱导的血小板聚集，动物实验表明其活性与临床一线药物相当，且不会显著延长出血时间，安全性高。本课题将AAP作为先导化合物，在现有临床药物构效关系的基础上，应用合理药物设计及计算机辅助药物设计中的药效团和分子对接技术对其进行结构优化，设计新化合物，进行活性筛选，并采用Biacore技术深入研究新化合物与GP IIb/IIIa受体分子的相互作用。期望能得出此类化合物的构效关系，寻找到1－2个抗血栓活性高，半衰期长的更适合临床应用的新化合物，为抗血栓药物的研究提供理论基础。

The binding of platelet GPIIb/IIIa and fibrinogen is the final pathway of platelets aggregation. The GPIIb/IIIa antagonist is one of the most efficacious antiplatelets aggregation drugs.AAP,discovered by our research group,is a GPIIb/IIIa antagonist,which has novel structure.It can efficiently inhibit platelets aggregation induced by PAF,ADP,collagen and thrombin.Experiments in vivo show that the pharmacological effect of AAP is equal to some first line drugs which are being uesd in clinical.Moreover,AAP does not lead to long-time bleeding. On the base of the relationship of structure and activity of clinical drugs,in the following research ,we will take AAP as a leading compound,take use of techniques of rational drug design and computer-aided drug design to design new compounds and then test their bioactivity in vivo and in vitro.The interaction between new compounds and GPIIb/IIIa will be explored by biacore system. By doing these experiments,we expect to find out the relationship between structure and activity of this kind of compounds,finding 1-2 novel compounds which own stronger antithrombotic activity ,longer half-life period and is more suitable for clinical application.The results would provide foundational theroy for the study of novel antithrombotic agents.