Topological Study of the Structures of Heterochiral Peptides Containing Equal Amounts of L-Leu and D-Leu

We designed and synthesized two dodecapeptides, Boc-(L-Leu-L-Leu-Aib-D-Leu-D-Leu-Aib)(2)-OMe (5) and Boc-L-Leu-L-Leu-Aib-(D-Leu-D-Leu-Aib)(2)-L-Leu-L-Leu-Aib-OMe (6), that contain equal amounts of L-Leu, D-Leu, and achiral Aib residues. The conformations of peptides 5 and 6 in the crystalline state were studied using X-ray crystallographic analysis. Peptide 5 formed a left-handed (M) alpha-helical structure, whereas peptide 6 was composed of a combination of fused (M) alpha-helical and right-handed (P) 3(10)-helical structures. In solution, roughly equivalent amounts of (P) and (M) helices were present in 5, whereas the (M) alpha-helix was present in 6 as its dominant conformation.