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

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.

Structural and conformational properties of (Z)-?-(1-naphthyl)- dehydroalanine residue

“…23. The ⌬ Z Nap residue was introduced by ring-opening Boc-Ala-⌬ Z Nap azlactone with amino group of Val-OMe.…”

“…Boc-Ala-⌬ Z Nap azlactone was prepared according to Ref. 23. To a solution of Boc-Ala-⌬ Z Nap azlactone (630 mg, 1.7 mmol) in THF (10 mL) was added HCl ⅐ H-Leu-OMe (1.8 mmol) and Nmethylmorphorine (NMM; 0.22 mL, 1.9 mmol) at 0°C.…”

“…The program PEPCON, written by M. Sisido (private communication) for a conformational energy calculation 29 and graphics 32 of a given peptide, was modified to be applicable to ␤-aryldehyroalanine-containing peptides. [23][24][25][33][34][35][36] …”

“…39 Solution conformation of peptide 1 was investigated using 1 H NMR spectroscopy. 23 The solvent accessibility of NH chemical shifts indicated that NH of Val residue participates in intramolecular hydrogen bonding. And a remarkable NOE (8.7%) was observed for the Ala C ␣ HO⌬ Z Nap NH proton pairs, suggesting that the protons are close to each other (Ͻ3 Å).…”

“…The synthesis and NMR study of peptide 1 have been reported earlier. 23 Also, to obtain additional information on ⌬ Z Napinduced conformations, hexapeptide 2 was synthesized and its solution conformation was investigated by 1 H-NMR spectroscopy:…”