Accommodation of a D-Phe residue into a right-handed 310-helix: Structure of Boc-D-Phe-(Aib)4-Gly-L-Leu-(Aib)2-Ome, an analogue of the amino terminal segment of antiamoebins and emerimicins

Abstract

The crystal structure of the nonapeptide Boc-D-Phe-Aib-Aib-Aib-Aib-Gly-Leu-Aib-AibOMe (I), which is an analogue of the N-terminal sequence of antiamoebins and emerimicins, establishes a completely 3₁₀-helical conformation with seven successive intramolecular 4 →1 hydrogen bonds. The average, Φ, ψ values for residues 1-8 are -59° and -32°, respectively. Crystal parameters are C₄₇H₇₇N₉O₁₂, space group P1, a = 10.636(4) Å, b = 11.239(4) Å, c = 12.227(6) Å, = 101.17(4)°, β = 97.22(4)°, = 89.80(3)°, Z = 1, R = 5.95% for 3018 data with |F0| > 3 α(F), resolution 0.93 Å. The use of the torsion angle k = C(i - 1)N(i)C^α(i)Cβ(i), where k = 68° for D-Phe and k = 164° for L-Leu, confirms the opposite configurations of these residues. The Φ, ψ values of -62° and -32° at D-Phe are unusual, since this region is characteristic of residues with L configurations. Peptide I possesses only two chiral residues of opposing configuration. The observed right-handed 3₁₀-helical structure suggests that helix sense has probably been determined by the stereo-chemical preferences of the Leu residue.