Design of peptides with α,β-dehydro-residues: synthesis, crystal structure and molecular conformation of a peptide N-tertiary-butyloxycarbonyl-_L -Leu-ΔPhe-_L -lle-OCH₃

Abstract

In order to develop new design rules with dehydro-residues a peptide tertiary-butyloxycarbonyl-_L -Leu-Δ Phe-_L -Ile-OCH₃ was synthesized. The synthesis was carried out in solution using azlactone procedure. The three-dimensional structure of the peptide was determined by X-ray diffraction method and refined to an R-factor of 0.065. The peptide adopts an unfolded S-shaped conformation with φ₁=-78.8(6)°, ψ₁=-28.5(7)°, φ₂=51.8(7)°, ψ₂=44.6(7)°, φ₃=-93.7(7)°, ψ₃^T=21.57°. This is the first example of a characteristic unfolded conformation of a peptide having ΔPhe at (i+2) position with a single branched β-carbon residue. The side chain conformation of Ile with χ^1,1=60.5(8)° χ^1,2=-66.7(7)° is not in a favourable form thus causing strong steric constraints. The crystal packing is stabilized by two intermolecular hydrogen bonds N₁-H₁O'₂=2.936(6) Å and N₃-H₃O'₁=3.096(6) Å and a number of van der Waals interactions involving side chains of Leu, ΔPhe and Ile as one block and the Boc groups from neighbouring peptide molecules as the second block.