Design of peptides with α,β-dehydro-residues: Synthesis and crystal structure of a tetrapeptide Boc-Ala-ΔPhe-ΔPhe-Phe-OCH₃

Abstract

In order to develop general rules of peptide design with α,β-dehydro-residues, a peptide, Boc-Ala-ΔPhe-ΔPhe-Phe-OCH₃, was synthesized. The peptide was crystallized from its solution in an acetone:water mixture (70:30). The crystals belong to orthorhombic space group P2₁2₁2₁ with a = 9.403(1) Å, b = 16.871(1) Å, c = 21.638(1) Å, and Z = 4. The peptide adopts a conformation with two overlapping types II' and III β-turns having dihedral angles, φ₁ = 53.7(6)°, ψ₁ = -135.9(4)°, φ₂ = -59.2(5)°, ψ₂ = -17.9(5)°, φ₃ = -68.4(5)°, ψ₃ = -18.8(6)°. The conformation was further characterized by two intramolecular 4 →1 hydrogen bonds involving imino nitrogen atoms of ΔPhe³ and Phe⁴ as donors and carbonyl oxygen atoms of blocking group Boc and Ala¹ as acceptors. The packing of the molecules in the unit cell is stabilized by an intermolecular hydrogen bond, N₂-H₂.s O'₃ [-x, y+1/2, -z+1/2] = 2.894 Å and van der Waals forces involving aromatic side chains.