Effect of side chains on turns and helices in peptides of beta3-aminoxy acids.

Abstract

We have investigated, using NMR, IR, and CD spectroscopy and X-ray crystallography, the conformational properties of peptides 1-10 of beta(3)-aminoxy acids (NH(2)OCHRCH(2)COOH) having different side chains on the beta carbon atom (e.g., R = Me, Et, COOBn, CH(2)CH(2)CH=CH(2), i-Bu, i-Pr). The beta N-O turns and beta N-O helices that involve a nine-membered-ring intramolecular hydrogen bond between NH(i)(+2) and CO(i), which have been found previously in peptides of beta(2,2)-aminoxy acids (NH(2)OCH(2)CMe(2)COOH), are also present in those beta(3)-aminoxy peptides. X-ray crystal structures and NMR spectral analysis reveal that, in the beta N-O turns and beta N-O helices induced by beta(3)-aminoxy acids, the N-O bond could be either anti or gauche to the C(alpha)-C(beta) bond depending on the size of the side chain; in contrast, only the anti conformation was found in beta(2,2)-aminoxy peptides. Both diamide 1 and triamide 9 exist in different conformations in solution and in the solid state: parallel sheet structures in the solid state and predominantly beta N-O turn and beta N-O helix conformations in nonpolar solvents. Theoretical studies on a series of model diamides rationalize very well the experimentally observed conformational features of these beta(3)-aminoxy peptides.