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. Another approach is to study the disintegrins. 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 preferred 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).
Williams
J A
JA
Protein Biochemistry, Thrombosis Research, Institute Emmanuel Kaye Building, Chelsea, London, England.
D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002449:Cell Aggregation / Q000187:drug effects / Q000502:physiology*; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides / Q000494:pharmacology / Q000502:physiology*; D010455:Peptides; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D013927:Thrombosis / Q000188:drug therapy; D014757:Viper Venoms / Q000494:pharmacology / Q000627:therapeutic use
D005343:Fibrinolytic Agents; D016023:Integrins; D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D014757:Viper Venoms; C057986:echistatin; C047981:arginyl-glycyl-aspartic acid