Enhanced beta-turn conformational stability of tripeptides containing Delta Phe in cis over trans configuration.

Conformations of three pairs of dehydropeptides with the opposite configuration of the Delta Phe residue, Boc-Gly-Delta(Z/E)Phe-Phe-p-NA (Z- p -NA and E- p -NA), Boc-Gly-Delta(Z/E)Phe-Phe-OMe (Z-OMe and E-OMe), and Boc-Gly-Delta(Z/E)Phe-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 beta-turn conformations and E-OMe and E-OH are unordered. There are two overlapping type III beta-turns in Z- p -NA, type II' beta-turn in E- p -NA, and type II beta-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, Delta(Z)Phe is a much stronger inducer of ordered conformations than Delta(E)Phe. It was also found that temperature coefficients of the amide protons are not reliable indicators of intramolecular hydrogen bonds donors in small peptides