Hydration and distortion of peptide helices in crystals. Alpha-helical structure of a dodecapeptide, Boc-(Ala-Leu-Aib)4-OMe.

The dodecapeptide Boc-(Ala-Leu-Aib)4-OMe crystallized with two independent helical molecules in a triclinic cell. The two molecules are very similar in conformation, with a 3(10)-helix turn at the N-terminus followed by an alpha-helix, except for an elongated N(7)...O(3) distance in both molecules. All the helices in the crystal pack in a parallel motif. Eleven water sites have been found in the head-to-tail region between the apolar helices that participate in peptide-water hydrogen bonds and a network of water-water hydrogen bonds. The crystal parameters are as follows: 2(C58H104N12O15)+ca. 10H2O, space group P1 with a = 12.946(2), b = 17.321(3), c = 20.465(4) A, alpha = 103.12(2), beta = 105.63(2), gamma = 107.50(2) degrees, Z = 2, R = 10.9% for 5152 data observed > 3 sigma (F), resolution 1.0 A. In contrast to the shorter sequences [Karle et al. (1988) Proc. Natl. Acad. Sci. USA 85, 299-303] and Boc-(Ala-Leu-Aib)2-OMe [Karle et al. (1989) Biopolymers 28, 773-781], no insertion of a water molecule into the helix is observed. However, the elongated N---O distance between Ala7 NH and Aib3 CO in both molecules (molecule A, 3.40 A; molecule B, 3.42 A) is indicative of an incipient break in the helices.