Design of peptides with α,β-dehydro-residues: syntheses, crystal structures and molecular conformations of two ΔPhe-Trp containing peptides

Abstract

The ΔPhe-Trp is a newly designed moiety that was found inducing a unique conformation in peptides. The peptides Boc-L-Val-ΔPhe-L-Trp-OCH₃ (I) and Boc-L-Leu-ΔPhe-L-Trp-OCH₃ (II) were synthesized by azlactone method in solution phase. The peptide (I) was crystallized from its solution in ethanol-water mixture in orthorhombic space group P2₁2₁2₁ with a=10.663(3) Å, b=11.204(3) Å, c=26.516(10) Å and peptide (II) was crystallized from its solution in acetone in a monoclinic space group P2₁ with a=9.354(1)Å, b=11.218(4)Å, c=15.633(1)Å and β=101.83(1)°. The structures were determined by direct methods. Peptide (I) was refined to an R value of 0.059 for 1554 observed reflections [I≥2σ (I)] and peptide (II) was refined to an R value of 0.043 for 2920 observed reflections [I≥2σ (I)]. The structures of peptides (I) and (II) were found to be identical. They formed an unusual type VIa β-turn conformation which is observed for the first time with a ΔPhe residue at (i+2) position indicating a unique influence of ΔPhe-Trp moiety in inducing a reproducible new structure in peptides.