Design of peptides with α,β-dehydro-residues: synthesis, crystal structure and molecular conformation of a tetrapeptide Z-ΔVal-Val-ΔPhe-Ile-Ome

Abstract

This is the first designed peptide with a combination of a branched β-carbon ΔVal and a ΔPhe residues. The peptide Z-ΔVal-Val-ΔPhe-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 P2₁2₁2₁ with a=12.513(2) Å, b=15.904(5) Å, c=17.686(2) Å 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 3₁₀-helical conformation with two intramolecular hydrogen bonds (i+3→i) involving carbonyl oxygen atoms of carbobenzoxy group and ΔVal and NH groups of ΔPhe and Ile with distances of 2.764(6) and 3.047(7) Å, respectively. The structure determination has revealed that a tetrapeptide with ÅVal at (i+1) and ΔPhe at (i+3) positions adopts a folded conformation despite the presence of unfavorable branched β-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 ΔVal and Val residues with carbonyl oxygen atoms of Val and ΔPhe residues belonging to a symmetry related molecule. The side chains of Val, ΔPhe and Ile form infinite chains of van der Waals interactions.