Further Evidence for 2-Alkyl-2-carboxyazetidines as γ-Turn Inducers

Reverse turns, it common motif in proteins and peptides, have attracted attention due to their relevance in it Wide variety of biological processes. In in attempt to artificially imitate and stabilize these turns in short peptides, we have developed versatile synthetic methodologies for the preparation of 2-alkyl-2-carboxyazetidines, and incorporated them into the i + 1 position of model tetrapeptides, where they have shown it tendency to induce gamma-turns However, to ascertain the general utility of these restricted amino acids its gamma-type reverse turn inducers, it was then required to study the conformational preferences when located at other positions. To this end, model tetrapeptides R-CO-Ala-Xaa-NHMe, containing differently Substituted azetidine moieties (Xaa = Aze, 2-MeAze, 2-BnAze) at the i + 2 position, were synthesized and Subjected to it thorough conformational analysis. The theoretical and experimental results obtained, including the X-ray diffraction structure of a dipeptide derivative containing this skeleton, provide evidence that the 2-alkyl-2-carboxyazetidine scaffold is able to efficiently induce gamma-turns when incorporated into these short peptides, irrespective of their localization in the peptide chain.