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.

A new synthetic route to (E)‐β‐phenyl‐α,β‐dehydroalanine (ΔEPhe)‐containing peptide was presented via photochemical isomerization of the corresponding (Z)‐β‐phenyl‐α,β‐dehydroalanine (ΔZPhe)‐containing peptide. By applying this method to Boc–Ala–ΔZPhe–Val–OMe (Z‐I: Boc, t‐butoxycarbonyl; OMe, methoxy), Boc–Ala–ΔEPhe–Val–OMe (E‐I) was obtained. The identification of peptide E‐I was evidenced by 1H‐nmr, 13C‐nmr, and uv absorption spectroscopy, elemental analysis, and hydrogenation. The conformation of peptide E‐Iin CDCl3 was investigated by 1H‐nmr spectroscopy (solvent dependence of NH chemical shift and difference nuclear Overhauser effect). Interestingly, peptide E‐I differed from peptide Z‐I in the hydrogen‐bonding mode. Namely, for peptide Z‐I, only Val NH participates in intramolecular hydrogen bonding, which leads to a type II β‐turn conformation supported by hydrogen bonding between CO(Boc) and NH(Val). On the other hand, for peptide E‐I, two NHs, ΔE Phe NH and Val NH, participate in intramolecular hydrogen bonding. In both peptides, a remarkable NOE (∼11–13%) was observed for Ala Cα H–ΔPhe NH pair. Based on the nmr data and conformational energy calculation, it should be concluded that peptide E‐I takes two consecutive γ‐turn conformations supported by hydrogen bonding between CO(Boc) and NH(ΔEPhe), and between CO(Ala) and NH(Val) as its plausible conformation. © 2000 John Wiley & Sons, Inc. Biopoly 53: 484–496, 2000