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

Abstract

A beta-hairpin conformation has been characterized in crystals of the decapeptide t-butoxycarbonyl-Leu-Val-beta Phe-Val-(D)Pro-Gly-Leu-beta Phe-Val-Val-methyl ester [beta Phe; (S)-beta(3) homophenylalanine] by x-ray diffraction. The polypeptide chain reversal is nucleated by the centrally positioned (D)Pro-Gly segment, which adopts a type-I' beta-turn conformation. Four intramolecular cross-strand hydrogen bonds stabilize the peptide fold. The beta Phe(3) and beta Phe(8) residues occupy facing positions on the hairpin, with the side chains projecting on opposite faces of the beta-sheet. At the site of insertion of beta-residues, the polarity of the peptide units along each strand reverses, as compared with the alpha-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 beta-sheet is formed by hydrogen bonding between strands of antiparallel pairs of beta-hairpins. The crystallographic parameters for C(65)H(102)N(10)O(13) x 3H(2)O are: space group P2(1)2(1)2(1); a = 19.059(8) A, b = 19.470(2) A, c = 21.077(2) A; Z = 4; agreement factor R(1) = 9.12% for 3,984 data observed >4 sigma(F) and a resolution of 0.90 A.