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

The cyclic peptide cyclo(Val-Leu-Leu-d-Phe-Pro)(2) (peptide 1) was specifically designed for structural chemistry investigations, drawing inspiration from Gramicidin S (GS). Previous studies have shown that Pro residues within 1 adopt a down-puckering conformation of the pyrrolidine ring. By incorporating fluoride-Pro with 4-trans/cis-isomers into 1, an up-puckering conformation was successfully induced. In the current investigation, introducing hy-droxy-prolines with 4-trans/cis-isomer configurations (tHyp/cHyp) into 1 gave cyclo(Val-Leu-Leu-d-Phe-tHyp)(2) methanol disolvate monohydrate, C(62)H(94)N(10)O(12)·2CH(4)O·H(2)O (4), and cyclo(Val-Leu-Leu-d-Phe-cHyp)(2) monohydrate, C(62)H(94)N(10)O(12)·H(2)O (5), respectively. However, the puckering of 4 and 5 remained in the down conformation, regardless of the geometric position of the hydroxyl group. Although the backbone structure of 4 with trans-substitution was asymmetric, the asymmetric backbone of 5 with cis-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.