Multivalent RGD synthetic peptides as potent alpha(V)beta(3) integrin ligands

We study herein the multivalency effect of a cluster of alpha(v)beta(3)-ligands held on a cyclodecapeptide template. An array of RAFT(c[-RGDfK-])(n) derivatives containing from one to sixteen clustered RGD motifs were synthesized and comparatively assayed in vitro on alpha(v)beta(3)-expressing cells. Efficient inhibition of the alpha(v)beta(3)-specific 23C6 monoclonal antibody fixation was observed with ligands displaying three and four copies of the cyclo[-RGDfK-] peptide.