Crystal structure of Boc-LAla-ΔPhe-ΔPhe-ΔPhe-ΔPhe-NHMe: a left-handed helical peptide

Abstract

αβ-Dehydrophenylalanine residues constrain the peptide backbone to β-bend conformation. A pentapeptide containing four consecutive (APhe) residues has been synthesised and crystallised. The peptide Boc-LAla-ΔPhe-ΔPhe-ΔPhe-ΔPhe-NHMe (C₄₅H₄₆N₆O₇, MW = 782.86) was crystallised from an acetonitrile/ methanol mixture. The crystal belongs to the orthorhombic space group P2₁2₁2₁ with a = 19.455(6), b = 20.912(9), c = 11.455(4) Å and Z = 4. The X-ray (MoK α , lD = 0.7107 Å) intensity data were collected using the Rigaku-AFC7 diffractrometer. The crystal structure was determined by direct methods and refined using the least-squares technique, R = 8.41% for 1827 reflections with ||F₀|| > 4σ||F_o||. The molecule contains the largest stretch of consecutive dehydrophenylalanine residues whose crystal structure has been determined so far. The peptide adopts left-handed 3₁₀-helical conformation despite the presence of LAla at the N-terminus. The mean ∅, ψ values, averaged across the last four residues are 56.8° and 17.5°, respectively. There are four 41 intramolecular hydrogen bonds, characteristic of the 3₁₀-helix. In the crystal each molecule interacts with four crystallographically symmetric molecules with one hydrogen bond each.