Unfolding of an α-helix in peptide crystals by solvation: Conformational fragility in a heptapeptide

The structure of the peptide Boc‐Val‐Ala‐Leu‐Aib‐Val‐Ala‐Leu‐OMe has been determined in crystals obtained from a dimethylsulfoxide–isopropanol mixture. Crystal parameters are as follows: C38H69N7O10 · H2O · 2C3H7OH, space group P21, a = 10.350 (2) Å, b = 26.084 (4) Å, c = 10.395(2) Å, β = 96.87(12), Z = 2, R = 8.7% for 2686 reflections observed > 3.0 σ (F). A single 5 → 1 hydrogen bond is observed at the N‐terminus, while two 4 → 1 hydrogen bonds characteristic of a 310‐helix are seen in the central segment. The C‐terminus residues, Ala(6) and Leu(7) are expended, while Val(5) is considerably distorted from a helical conformation. Two isopropanol molecules make hydrogen bonds to the C‐terminal segment, while a water molecule interacts with the N‐terminus. The structure is in contrast to that obtained for the same peptide in crystals from methanol‐water [ I. L. Karle, J. L. Flippen‐Anderson, K. Uma, and P. Balaram (1990) Proteins: Structure, Function and Genetics, Vol. 7, pp. 62–73] in which two independent molecules reveal an almost perfect α‐helix and a helix penetrated by a water molecule. A comparison of the three structures provides a snapshot of the progressive effects of solvation leading to helix unwinding. The fragility of the heptapeptide helix in solution is demonstrated by nmr studies in CDC13 and (CD3)2SO. A helical conformation is supported in the apolar solvent CDCl3, whereas almost complete unfolding is observed in the strongly solvating medium (CD3)2SO. © 1993 John Wiley & Sons, Inc.