Peptide hybrids containing α- and β-amino acids: structure of a decapeptide β-hairpin with two facing β-phenylalanine residues

Abstract

A β-hairpin conformation has been characterized in crystals of the decapeptide t-butoxycarbonyl-Leu-Val-βPhe-Val-^DPro-Gly-Leu-βPhe- Val-Val-methyl ester [βPhe; (S)-β³ homophenylalanine] by x-ray diffraction. The polypeptide chain reversal is nucleated by the centrally positioned ^DPro-Gly segment, which adopts a type-I′ β-turn conformation. Four intramolecular cross-strand hydrogen bonds stabilize the peptide fold. The βPhe(3) and βPhe(8) residues occupy facing positions on the hairpin, with the side chains projecting on opposite faces of the β-sheet. At the site of insertion of β-residues, the polarity of the peptide units along each strand reverses, as compared with the a-peptide segments. In this analog, a small segment of a polar sheet is observed, where adjacent CO and NH groups line up in opposite directions in each strand. In the crystal, an extended β-sheet is formed by hydrogen bonding between strands of antiparallel pairs of β-hairpins. The crystallographic parameters for C₆₅H₁₀₂N₁₀O₁₃ 3H₂O are: space group P2₁2₁2₁; a = 19.059(8) Å, b = 19.470(2) Å, c = 21.077(2) Å; Z = 4; agreement factor R₁ = 9.12% for 3,984 data observed >4σ(F) and a resolution of 0.90 Å.