Monomeric and Dimeric Disintegrins: Platelet Active Agents from Viper Venom

When the term “disintegrin” was first coined in 1990, it described a family of naturally occurring proteins with low molecular weights and highly conserved sequences, both in their cysteine arrangements and adhesive Arg-Gly-Asp (RGD) motifs. Another common characteristic was the inhibitory potential these proteins demonstrated in interacting with cell-surface integrin receptors. Measurement of the effect by disintegrins on the interaction between the platelet receptor αIIbβ3 and its ligand, fibrinogen, has become a hallmark assay for comparing the activities of members of this increasingly diverse family discovered in the past two decades. This review focuses on the inhibitory profiles, based on platelet function, of the monomeric and heterodimeric disintegrins described to date, as well as the informative contributions of disintegrin mutations in our understanding of the structure–function relationships between ligand and αIIbβ3. The challenge of naming future examples of these proteins is also addressed.