Solution structures and integrin binding activities of an RGD peptide withtwo isomers

The Arg-Gly-Asp (RGD) sequence serves as the primary integrin recognition s ite in extracellular matrix proteins, and peptides containing this sequence can mimic the activities of the matrix proteins. Depending on the context of the RGD sequence, an RGD-containing peptide may bind to all of the RGD-d irected integrins, to a few, or to only a single one. We have previously is olated from a phage-displayed peptide library a cyclic peptide that binds a vidly to the alpha (v)beta (3) and alpha (v)beta (5) integrins but does not bind to other closely related integrins. This peptide, ACDCRGDCFCG, exists in two natural configurations depending on internal disulfide bonding. The peptide with the 1-4: 2-3 disulfide bond arrangement accounts for most of the alpha (v) integrin binding activity, whereas the 1-3; 2-3 peptide is ab out 10-fold less potent. Solution structure analysis by nuclear magnetic re sonance reveals an entirely different presentation of the RGD motif in the two isomers of RGD-4C. These results provide new insight into the ligand re cognition specificity of integrins.