NMR analysis of a conformational transition in an acyclic peptide. Model system for studying helix unfolding

Abstract

The stabilization of helical structures in short apolar peptides is readily achieved by introduction of α,α-dialkylamino acids. The use of stereochemically constrained residues in conjunction with conformationally flexible segments permits the design of peptides that are poised to undergo structural transitions. The octapeptide Boc-Leu-Ac₈c-Val-Gly-Gly-Leu-Ac₈c-Val-OMe (Ac₈c = 1-aminocyclooctane-1-carboxylic acid) incorporates residues with contradictory conformational tendencies. NMR analysis in CDCl₃, using nuclear Overhauser effects and delineation of hydrogen-bonded NH groups establishes a 3₁₀-helical conformation. In a polar strongly solvating medium, like DMSO, the helix unfolds. Studies in CDCl₃/DMSO mixtures provide clear evidence for a solvent dependent conformational transition. Amide NH chemical shifts and temperature coefficients at varying solvent composition allow a detailed structural analysis of the unfolding process. The intrinsic fragility of the octapeptide helix provides an opportunity to examine invasion of the helix backbone by water molecules. Studies in DMSO solution containing low concentrations of water establish that preferential water peptide interactions may indeed be present.