Design of peptides with a,b-dehydro-residues: Syntheses, crystal structures and molecular conformations of two DPhe-Trp containing peptides

Vijayaraghavan Rangachari, University of Southern Mississippi
J. Makker, All India Institute of Medical Sciences
P. Kumar, All India Institute of Medical Sciences
S. Dey, All India Institute of Medical Sciences
Tej P. Singh, All India Institute of Medical Sciences

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.