Cyclic analogues of bioactive peptides

Also involved: R. De Marco

Cyclic peptides have been widely utilized as templates for the design of different kinds of turn-like structures. In particular, several examples of cyclic, bicyclic or spirocyclic peptidomimetic and non-peptidic scaffolds have been reported in the literature as turn mimicking structures.  Our interest is focused on the design, synthesis and conformational analysis of cyclotetrapeptides and  partially modified retro-inverso (PMRI)-cyclotetrapeptide models, with a predictable 3D display of the side chains, useful for targeting specific bioactive conformations.  As prototypic examples, we studied the models for testing some selected, novel RGD peptidomimetic compounds capable to interfere with integrin receptors and cyclic analogues of the tetrapeptides endomorphin-1 (EM-1, H-Tyr-Pro-Trp-Phe-NH2, and endomorphin-2 (EM-2, H-Tyr-Pro-Phe-Phe-NH2),  that have been found to activate μ-opioid receptor (MOR) with high affinity and selectivity.

References

• Gentilucci, L.; Cardillo, G.; Spampinato, S.; Tolomelli, A.; Squassabia, F.; De Marco, R.; Bedini, A.; Baiula, M.; Belvisi, L.; Civera, M.. "Antiangiogenic Effect of Dual/Selective α 5β 1/α vβ 3 Integrin Antagonists Designed on Partially Modified Retro-Inverso Cyclotetrapeptide Mimetics" J. Med. Chem. 2010, 53,  106-118.
• Gentilucci, L.; Cardillo, G.; Tolomelli, A.; De Marco, R.; Garelli, A.; Spampinato, S.; Sparta, A.; Juaristi, E. "Synthesis and Conformational Analysis of Cyclotetrapeptide Mimetic β-Turn Templates and Validation as 3D Scaffolds"  ChemMedChem 2009, 4,  517-523.