Enhanced β-turn conformational stability of tripeptides containing Δphe in cis over trans configuration

Conformations of three pairs of dehydropeptides with the opposite configuration of the ΔPhe residue, Boc-Gly-Δ^Z/EPhe-Phe-p- NA (Z- p -NA and E- p -NA), Boc-Gly-Δ^Z/EPhe-Phe-OMe (Z-OMe and E-OMe), and Boc-Gly-Δ^Z/EPhe-Phe-OH (Z-OH and E-OH) were compared on the basis of CD and NMR studies in MeOH, TFE, and DMSO. The CD results were used as the additional input data for the NMR-based calculations of the detailed solution conformations of the peptides. It was found that Z- p -NA, E- p -NA, Z-OMe, and Z-OH adopt the β-turn conformations and E-OMe and E-OH are unordered. There are two overlapping type III β-turns in Z- p -NA, type II' β-turn in E- p -NA, and type II β-turn in Z-OMe and Z-OH. The results obtained indicate that in the case of methyl esters and peptides with a free carboxyl group, Δ^ZPhe is a much stronger inducer of ordered conformations than Δ^EPhe. It was also found that temperature coefficients of the amide protons are not reliable indicators of intramolecular hydrogen bonds donors in small peptides.