ANTITHROMBOTIC AGENTS - FROM RGD TO PEPTIDE MIMETICS

被引：138

作者：

OJIMA, I ^{[1
]}

CHAKRAVARTY, S ^{[1
]}

DONG, Q ^{[1
]}

机构：

[1] SUNY STONY BROOK, DEPT CHEM, STONY BROOK, NY 11794 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 1995年 / 3卷 / 04期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/0968-0896(95)00036-G

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

This review covers the recent advances in the development of highly potent inhibitors of platelet aggregation as potential therapeutic drugs for thrombosis related to cardiovascular and cerebrovascular diseases. The discovery of RGD sequence-directed cell surface receptors (the integrins) has led to extensive research in the development of small RGD containing peptides and their mimetics as:antithrombotic agents. These agents work by inhibiting platelet aggregation through competitive blocking of fibrinogen to the platelet surface receptor, GPIIb/IIIa. The pharmacophoric nature of the aspartic acid and arginine side chains of the RGD unit has allowed the development of strategies for rational design, largely based on assumed bioactive RGD conformations and lead optimization. Applications of such strategies, from RGD peptides to peptide hybrids and then to non-peptide mimetics, are described. Also discussed is the important issue of specificity toward GPIIb/IIIa, keeping in view that the RGD unit is a key recognition signal for a variety of cell surface receptors.

引用

页码：337 / 360

页数：24

共 142 条

[21] DESIGN AND SYNTHESIS OF A C-7 MIMETIC FOR THE PREDICTED GAMMA-TURN CONFORMATION FOUND IN SEVERAL CONSTRAINED RGD ANTAGONISTS [J].