Solid-phase synthesis of cyclic RGD-furanoid sugar amino acid peptides as integrin inhibitors

The solid-phase synthesis of cyclic RGD peptides containing either one or two furanoid sugar amino acids (SAAs) is reported. Using a cyclization-cleavage approach five peptides were successfully assembled and consecutively tested on their ability to bind to the integrin receptors α vβ 3 and α IIbβ 3. The cyclic tetrapeptide c[RGD-SAA] ( 1) showed the most promising activity in an inhibition assay with an IC 50 of 1.49 μM for the α vβ 3 receptor and 384 nM for the α IIbβ 3 receptor. Novel cyclic RGD peptides containing one or two furanoid sugar amino acids were synthesized via a cyclization-cleavage approach using Kaiser's oxime resin. Evaluation of their ability to bind to the integrin receptors α vβ 3 and α IIbβ 3 revealed that compound 1 has the highest affinity for both receptors.