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.