Peptide design 3₁₀-helical conformation of a linear pentapeptide containing two dehydrophenylalanines, Boc-Gly-Δ^ZPhe-Leu-Δ^ZPhe-Ala-NHCH₃

Abstract

α,β-Dehydroamino acids are expected to provide conformational constraint to the peptide backbone. A pentapeptide containing two dehydrophenylalanines (Δ^ZPhe) separated by one L-amino acid has been synthesized and its solid state conformation determined. The pentapeptide, Boc-Gly-Δ^ZPhe-Leu-Δ^ZPhe-Ala-NHCH₃, crystallizes from aqueous methanol in the orthorhombic space group P2₁2₁2₁. There are four formula units, C₃₅H₄₆N₆O₇, in a unit cell of dimensions a = 10.155(3), b = 15.175(1), and c = 23.447(2) Å, at room temperature. The structure was solved by direct methods program, SIR88, and refined to a final R = 0.038 based on 3049 reflections with I >2σ(I). All the peptide links are trans and the backbone conformation of the pentapeptide can be described as a 3₁₀-helix, with mean Φ, ψ values of −65.1° and −22.8° (the value is averaged over the first four residues). There are four intramolecular 4 → 1 type hydrogen bonds characteristic of 3₁₀-type helices. In the crystal, the helices are held together by intermolecular N-H^...O=C head-to-tail and lateral hydrogen bonding between symmetry related molecules. This mode of packing is similar to the packing motifs observed so often in other oligopeptides that adopt a 3₁₀-helical structure.