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 indep endent helical molecules in a triclinic cell. The two molecules are ve ry 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) distan ce in both molecules. All the helices in the crystal pack in a paralle l 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 parame ters are as follows: 2(C58H104N12O15)+ca. 10H(2)O, space group P1 with a = 12.946(2), b = 17.321(3), c = 20.465(4) Angstrom, alpha = 103.12( 2), beta = 105.63(2), gamma = 107.50(2)degrees, Z = 2, R = 10.9% for 5 152 data observed > 3 sigma(F), resolution 1.0 Angstrom. In contrast t o 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) Biopol ymers 28, 773-781], no insertion of a water molecule into the helix is observed. However, the elongated N---O distance between Ala(7) NH and Aib(3) CO in both molecules (molecule A, 3.40 Angstrom; molecule B, 3 .42 Angstrom) is indicative of an incipient break in the helices. (C) Munksgaard 1994.