SOLID-STATE AND SOLUTION CONFORMATIONS OF A HELICAL PEPTIDE WITH A CENTRAL GLY-GLY SEGMENT

The influence of amino acids with contrasting conformational tendencie s on the stereochemistry of oligopeptides has been investigated using an octapeptide Boc-Leu-Aib-Val-Gly-Gly-Leu-Aib-Val-OMe, which contains two helix-promoting Aib residues and a central helix-destabilizing Gl y-Gly segment. Single crystal x-ray diffraction studies reveal that a 3(10)-helix a formed up to the penultimate Aib residue, at which point there is a helix reversal in the backbone, reminiscent of a C-termina l 6 --> 1 hydrogen bond. The curious feature in the crystal is the sol vation of the possible 6 --> 1 bond by a Ch(3)OH molecule, where the O H is inserted between O(3) and N(8) and participates in hydrogen bonds with both. The cell parameters are as follows: space group P2(1)2(1)2 (1), a = 10.649(4) Angstrom, b = 15.694(5) Angstrom, c = 30.181(8) Ang strom, R = 6.7% for 3427 data (\F-0\ > 3 sigma F) observed to 0.9 Angs trom. Nuclear magnetic resonance studies in CDCl3 using NH group solve nt accessibility and nuclear Overhauser effects as probes are consiste nt with a 3(10)-helical conformation. In contrast, in (CD3)(2)SO, unfo lding of the central segment results in a multiple beta-turn structure , with beta-turn conformations populated at residues 1-2, 3-4, and 6-7 . CD studies in methanol-2,2,2-trifluoroethanol (TFE) mixtures also pr ovide evidence for a solvent-dependent structural transition. Helical conformations are populated in TFE, while type II beta-turn structures are favored in methanol. (C) 1996 John Wiley & Sons, Inc.