In vitro and in vivo properties of NSL-9511, a novel anti-platelet hexapeptide without an RGD sequence

Integrins are heterodimeric cell surface receptor molecules and are thought to be particularly important mediators of cell adhesion to extracellular matrix proteins, cell migration, cell-to-cell contact, etc. Many of them, such as platelet GpIIb/IIIa (fibrinogen receptor), vitronectin receptor and fibronectin receptor recognize the Arg-GlyAsp sequence (RGD) as a common recognition motif within their putative ligands [1,2]. Because the RGD sequence has been found in many types of proteins, there are apparent redundancies in integrin-ligand interactions. These redundancies are interesting aspects of integrin receptors and may be beneficial to cell functions. We are developing small peptides which are specific for each integrin as a tool for investigating ligand-integrin interactions and as agents for therapeutic uses. In this study, we have found a novel motif sequence which exhibited potent and highly specific GpIIb/IIIa antagonistic activity. In vivo and in vitro properties of one of these motif peptides are examined and discussed.