PEPTIDE MIMICS FOR STRUCTURAL FEATURES IN PROTEINS - CRYSTAL-STRUCTURES OF 3 HEPTAPEPTIDE HELICES WITH A C-TERMINAL 6-]1 HYDROGEN-BOND

The crystal structure determination of three heptapeptides containing alpha-aminoisobutyryl (Aib) residues as a means of helix stabilization provides a high-resolution characterization of 6 --> 1 hydrogen-bonde d conformations, reminiscent of helix-terminating structural features in proteins. The crystal parameters for the three peptides, Boc-Val-Ai b-X-Aib-Ala-Aib-Y-OMe, where X and Y are Phe, Leu (I), Leu, Phe (II) a nd Leu, Leu (III) are: (1) space group P1, Z = 1, a = 9.903 angstrom, b = 10.709 angstrom, c = 11.969 angstrom, alpha = 102.94-degrees, beta = 103.41-degrees, gamma = 92.72-degrees, R = 4.55%; (II) space group P2(1), Z = 2, a = 10.052, b = 17.653 angstrom, c = 13.510 angstrom, be ta = 108.45-degrees, R = 4.49%; (III) space group P1, Z = 2 (two indep endent molecules IIIa and IIIb in the asymmetric unit), a = 10.833 ang strom, b = 13.850 angstrom, c = 16.928 angstrom, alpha = 99.77-degrees , beta = 105.90-degrees, gamma = 90.64-degrees, R = 8.54%. In all case s the helices form 3(10)/alpha-helical (or 3(10)-helical) structures, with helical columns formed by head-to-tail hydrogen bonding. The heli ces assemble in an all-parallel motif in crystals I and III and in an antiparallel motif in II. In the four crystallographically characteriz ed molecules, I, II, IIIa and IIIb, Aib(6) adopts a left-handed helica l (h(L)) conformation with positive phi, psi values, resulting in 6 -- > 1 hydrogen-bond formation between Aib(2) CO and Leu(7)/Phe(7) NH gro ups. In addition a 4 --> 1 hydrogen bond is seen between Aib(3) CO and Aib(6) NH groups. This pattern of hydrogen bonding is often observed at the C-terminus of helices in proteins, with the terminal pi-type tu rn being formed by four residues adopting the h(R)h(R)h(R)h(L) conform ation. (C) Munksgaard 1993.