Acta Crystallographica Section E: Crystallographic Communications (Sep 2024)

Puckering effects of 4-hydroxy-l-proline isomers on the conformation of ornithine-free Gramicidin S

  • Akiko Asano,
  • Kanako Nakayama,
  • Sakura Okada,
  • Takuma Kato,
  • Mitsunobu Doi

DOI
https://doi.org/10.1107/S2056989024007771
Journal volume & issue
Vol. 80, no. 9
pp. 942 – 946

Abstract

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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 hydroxyprolines with 4-trans/cis-isomer configurations (tHyp/cHyp) into 1 gave cyclo(Val-Leu-Leu-D-Phe-tHyp)2 methanol disolvate monohydrate, C62H94N10O12·2CH4O·H2O (4), and cyclo(Val-Leu-Leu-D-Phe-cHyp)2 monohydrate, C62H94N10O12·H2O (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 anticipated influence of stress from the geometric positioning, which was expected to affect the puckering, may have been mitigated by interactions between the hydroxyl groups of hydroxyproline, the solvent molecules, and peptides.

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