DISINTEGRINS - RGD-CONTAINING PROTEINS WHICH INHIBIT CELL MATRIX INTERACTIONS (ADHESION) AND CELL CELL-INTERACTIONS (AGGREGATION) VIA THE INTEGRIN RECEPTORS

Whereas many attempts have been made to generate synthetic, high affinity, linear RGD-peptides (Arginine-Glycine-Aspartic acid), by analogy with glycoprotein ligands to integrins, success has been limited. What has emerged is that the stereochemistry of the Arg-Gly-Asp-X (RGDX) recognition sequence is essential to ligand binding. This has led to the study of small, chemically synthesised, cyclic-RGD peptides [1]. Another approach is to study the disintegrins [2, 3, 4, 5, 6, 7, 8]. These high-affinity RGD-polypeptides (50-90 KDa) from viper venoms are << natural >> ligands to integrins, presumably as inhibitors of physiological ligands such as fibrinogen. A study of the disintegrins may shed some light on the prefered conformation of the active form of RGD, as well as the contribution of other potential recognition motifs in these molecules to modulate RGD interactions with receptors (fig. 1).