Synthesis, and crystal and molecular structure of the 3₁₀-helical α,β-dehydro pentapeptide Boc-Leu-Phe-Ala-ΔPhe-Leu-Ome

Abstract

αβ-Dehydro amino acid residues are known to constrain the peptide backbone to the β -bend conformation. A pentapeptide containing only one α ,β dehydrophenylalanine (ΔPhe) residue has been synthesized and crystallized, and its solid state conformation has been determined. The pentapeptide Boc-Leu-Phe-Ala-ΔPhe-Leu-OMe (C₃₉H₅₅N₅O₈, M_w = 721.9) was crystallized from aqueous methanol. Monoclinic space group was P2₁, a = 10.290(2)°, b = 17.149(2)°, c = 12.179(2) Å, β = 96.64(1)° with two molecules in the unit cell. The X-ray (Mo K α, λ = 0.7107A) intensity data were collected using a CAD4 diffractometer. The crystal structure was determined by direct methods and refined using least-squares technique. R = 4.4% and R_w = 5.4% for 4403 reflections having |F₀| ≥3σ(|F₀|). All the peptide links are trans and the pentapeptide molecule assumes 3₁₀-helical conformation. The mean Φψ values, averaged over the first four residues, are −64.4°, −22.4° respectively. There are three 4 →1 intramolecular hydrogen bonds, characteristic of 3₁₀,-helix. In the crystal, the peptide helices interact through two head-to-tail. N-H-O intermolecular hydrogen bonds. The peptide molecules related by 2₁, screw symmetry form a skewed assembly of helices.