NMR ANALYSIS OF A CONFORMATIONAL TRANSITION IN AN ACYCLIC PEPTIDE - MODEL SYSTEM FOR STUDYING HELIX UNFOLDING

The stabilization of helical structures in short apolar peptides is re adily achieved by introduction of alpha,alpha-dialkylamino acids. The use of stereochemically constrained residues in conjunction with confo rmationally flexible segments permits the design of peptides that are poised to undergo structural transitions. The octapeptide Boc-Leu-Ac(8 )c-Val-Gly-Gly-Leu-Ac(8)c-Val-OMe (Ac(8)c = 1-aminocyclooctane-1-carbo xylic acid) incorporates residues with contradictory conformational te ndencies. NMR analysis in CDCl3, using nuclear Overhauser effects and delineation of hydrogen-bonded NH groups establishes a 3(10)-helical c onformation. In a polar strongly solvating medium, like DMSO, the heli x 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 d etailed structural analysis of the unfolding process. The intrinsic fr agility of the octapeptide helix provides an opportunity to examine in vasion of the helix backbone by water molecules. Studies in DMSO solut ion containing low concentrations of water establish that preferential water peptide interactions may indeed be present.