CONFORMATIONAL PREFERENCE IN BETA-ARYLDEHYDROALANINE - SYNTHESIS AND CONFORMATIONAL STUDY OF TRIPEPTIDES CONTAINING BETA-ARYLDEHYDROALANINERESIDUES

In order to investigate the effect of bulky beta-substituents on the c onformational preference in alpha,beta-dehydroamino acid residues, thr ee kinds of tripeptides containing (Z)-beta-phenyldehydroalanine, (Z)- beta-(1-naphthyl)dehydroalanine, or (Z)-beta-(1-pyrenyl)dehydroalanine residue were synthesized: Boc-Ala-Delta(Z)AA-Val-OMe (Boc, t-butoxyca rbonyl; Ala, L-alanine; Delta(Z)AA, (Z)-beta-aryldehydroalanine; Val, L-valine; OMe, methoxy). Their conformations in solution were investig ated using H-1 NMR spectroscopy. The solvent accessibility of the NH r esonances and the nuclear Overhauser effect (NOE) indicated that the t hree peptides in CDCl3 form a type II beta-turn conformation supported by hydrogen bonding between CO (Boc) and NH (Val). From a conformatio nal energy calculation, the three kinds of Delta(Z)AA residues were al so shown to favor a type II beta-turn conformation. In each beta-turn, the orientation of the aryl plane was found to be non planar relative to the C-alpha=C-beta-C-gamma plane, suggesting that a steric interac tion between the P-aryl group and the peptide backbone leads to the in ternal rotation angles preferred for the beta-turn backbone.