Ruoslahti E
La Jolla Cancer Research Center, Burnham Institute, California 92037, USA.
Annu Rev Cell Dev Biol. 1996;12:697-715. doi: 10.1146/annurev.cellbio.12.1.697.
Proteins that contain the Arg-Gly-Asp (RGD) attachment site, together with the integrins that serve as receptors for them, constitute a major recognition system for cell adhesion. The RGD sequence is the cell attachment site of a large number of adhesive extracellular matrix, blood, and cell surface proteins, and nearly half of the over 20 known integrins recognize this sequence in their adhesion protein ligands. Some other integrins bind to related sequences in their ligands. The integrin-binding activity of adhesion proteins can be reproduced by short synthetic peptides containing the RGD sequence. Such peptides promote cell adhesion when insolubilized onto a surface, and inhibit it when presented to cells in solution. Reagents that bind selectively to only one or a few of the RGD-directed integrins can be designed by cyclizing peptides with selected sequences around the RGD and by synthesizing RGD mimics. As the integrin-mediated cell attachment influences and regulates cell migration, growth, differentiation, and apoptosis, the RGD peptides and mimics can be used to probe integrin functions in various biological systems. Drug design based on the RGD structure may provide new treatments for diseases such as thrombosis, osteoporosis, and cancer.
含有精氨酸-甘氨酸-天冬氨酸（RGD）附着位点的蛋白质，以及作为它们受体的整合素，构成了细胞黏附的主要识别系统。RGD序列是大量黏附性细胞外基质、血液和细胞表面蛋白的细胞附着位点，在已知的20多种整合素中，近一半在其黏附蛋白配体中识别该序列。其他一些整合素则与其配体中的相关序列结合。黏附蛋白的整合素结合活性可以通过含有RGD序列的短合成肽来重现。当这些肽固定在表面时可促进细胞黏附，而以溶液形式呈现给细胞时则抑制细胞黏附。通过围绕RGD将具有选定序列的肽环化以及合成RGD模拟物，可以设计出仅选择性结合一种或几种RGD导向整合素的试剂。由于整合素介导的细胞附着影响和调节细胞迁移、生长、分化和凋亡，RGD肽和模拟物可用于探究各种生物系统中的整合素功能。基于RGD结构的药物设计可能为血栓形成、骨质疏松症和癌症等疾病提供新的治疗方法。
