Conformational Preference in β-Aryldehydroalanine. Synthesis and Conformational Study of Tripeptides Containing β-Aryldehydroalanine Residues

Abstract

Abstract In order to investigate the effect of bulky β-substituents on the conformational preference in α, β-dehydroamino acid residues, three kinds of tripeptides containing (Z)-β-phenyldehydroalanine, (Z)-β-(1-naphthyl)dehydroalanine, or (Z)-β-(1-pyrenyl)dehydroalanine residue were synthesized: Boc–Ala–ΔZAA–Val–OMe (Boc, t-butoxycarbonyl; Ala, L-alanine; ΔZAA, (Z)-β-aryldehydroalanine; Val, L-valine; OMe, methoxy). Their conformations in solution were investigated using 1H NMR spectroscopy. The solvent accessibility of the NH resonances and the nuclear Overhauser effect (NOE) indicated that the three peptides in CDCl3 form a type II β-turn conformation supported by hydrogen bonding between CO (Boc) and NH (Val). From a conformational energy calculation, the three kinds of ΔZAA residues were also shown to favor a type II β-turn conformation. In each β-turn, the orientation of the aryl plane was found to be non planar relative to the Cα=Cβ–Cγ plane, suggesting that a steric interaction between the β-aryl group and the peptide backbone leads to the internal rotation angles preferred for the β-turn backbone.