Design of peptides with alpha,beta-dehydro-residues: synthesis, crystal structure and molecular conformation of a tetrapeptide Z-Delta Val-Val-Delta Phe-Ile-Ome

摘要

This is the first designed peptide with a combination of a branched beta-carbon DeltaVal and a DeltaPhe residues. The peptide Z-DeltaVal-Val-DeltaPhe-Ile-Ome was synthesized in solution phase. Single crystals were grown by slow evaporation from its solution in acetone-water mixture at 25 C. The crystals belong to an orthorhombic space group P2(1)2(1)2(1) with a = 12.513(2) Angstrom, b = 15.904(5) Angstrom, c = 17.686(2) Angstrom and Z = 4. The structure was determined by direct methods and refined by least-squares procedure to an R factor of 0.082. The peptide adopts a 3(10)-helical conformation with two intramolecular hydrogen bonds (i + 3 --> i) involving carbonyl oxygen atoms of carbobenzoxy group and DeltaVal and NH groups of DeltaPhe and Ile with distances of 2.764(6) and 3.047(7) Delta, respectively. The structure determination has revealed that a tetrapeptide with DeltaVal at (i + 1) and DeltaPhe at (i + 3) positions adopts a folded conformation despite the presence of unfavorable branched beta-carbon residues Val and Ile at (i + 2) and (i + 4) positions, respectively. The packing of the molecules in the unit cell is stabilized by two intermolecular hydrogen bonds involving NH groups of DeltaVal and Val residues with carbonyl oxygen atoms of Val and DeltaPhe residues belonging to a symmetry related molecule. The side chains of Val, DeltaPhe and Ile form infinite chains of van der Waals interactions. (C) 2003 Elsevier Science B.V. All rights reserved. [References: 12]