Solid state and solution conformations of a helical peptide with a central gly‐gly segment

The influence of amino acids with contrasting conformational tendencies 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 Gly‐Gly segment. Single crystal x‐ray diffraction studies reveal that a 3 10 ‐helix is formed up to the penultimate Aib residue, at which point there is a helix reversal in the backbone, reminiscent of a C‐terminal 6 → I hydrogen bond. The curious feature in the crystal is the solvation of the possible 6 → 1 bond by a CH 3 OH molecule, where the OH 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) Å, b = 15.694(5) Å, c = 30.181(8) Å, R = 6.7% for 3427 data (| F 0 | > 3σF) observed to 0.9 Å. Nuclear magnetic resonance studies in CDCl 3 using NH group solvent accessibility and nuclear Overhauser effects as probes are consistent with a 3 10 ‐helical conformation. In contrast, in (CD 3 ) 2 SO, unfolding of the central segment results in a multiple β‐turn structure, with β‐turn conformations populated at residues 1–2, 3–4, and 6–7. CD studies in methanol‐2,2,2‐trifluoroethanol (TFE) mixtures also provide evidence for a solvent‐dependent structural transition. Helical conformations are populated in TFE, while type II β‐turn structures are favored in methanol. © 1996 John Wiley & Sons, Inc.