New cyclic RGD peptides: synthesis, characterization, and theoretical activity towards αvβ3 integrin

Two new cyclic RGD peptides were prepared using a click chemistry approach. The linear RGDfV peptide was synthesized by solid-phase peptide synthesis using a 9-fluorenylmetoxicarbonyl (Fmoc) strategy and a 2-chlorotrityl chloride resin. After coupling 5-hexynoic acid the peptide was cleaved from the resin and linked to propargylamine. The bis-alkynyl RGDfV peptide was then reacted with two different bis-azides by treatment with copper iodide and triethylamine. These two cyclic RGD peptides were characterized by NMR and HRMS. In order to evaluate the interaction of these new compounds with integrin αvβ3 docking experiments were carried out and the results compared with those obtained with cyclo(RGDf[N-Me]V) (Cilengitide). The two new cyclic RGD peptides showed a higher affinity to the αvβ3 integrin when compared with Cilengitide thus representing two new potential integrin αvβ3 antagonists.

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