Puckering effects of 4-hy-droxy-l-proline isomers on the conformation of ornithine-free Gramicidin S.

The cyclic peptide (Val-Leu-Leu-d-Phe-Pro) (peptide ) was specifically designed for structural chemistry investigations, drawing inspiration from Gramicidin S (GS). Previous studies have shown that Pro residues within adopt a down-puckering conformation of the pyrrolidine ring. By incorporating fluoride-Pro with 4-/-isomers into , an up-puckering conformation was successfully induced. In the current investigation, introducing hy-droxy-prolines with 4-/-isomer configurations (tHyp/cHyp) into gave (Val-Leu-Leu-d-Phe-tHyp) methanol disolvate monohydrate, CHNO·2CHO·HO (), and (Val-Leu-Leu-d-Phe-cHyp) monohydrate, CHNO·HO (), respectively. However, the puckering of and remained in the down conformation, regardless of the geometric position of the hydroxyl group. Although the backbone structure of with -substitution was asymmetric, the asymmetric backbone of with -substitution was unexpected. It is speculated that the anti-cipated influence of stress from the geometric positioning, which was expected to affect the puckering, may have been mitigated by inter-actions between the hydroxyl groups of hy-droxy-proline, the solvent mol-ecules, and peptides.