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

Abstract

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 310-helix turn at the N-terminus followed by an -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)Å, =103.12(2), β= 105.63(2), = 107.50(2)°, Z= 2, R= 10.9% for 5152 data observed > 3s(F), resolution 1.0 Å. In contrast to the shorter sequences [Karle et al. (1988) Proc. Natl. Acad. Sci. USA85, 299-3031 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 Å; molecule B, 3.42 Å) is indicative of an incipient break in the helices.