Effect of side chains on turns and helices in peptides of β 3-aminoxy acids

Abstract

We have investigated, using NMR, IR, and CD spectroscopy and X-ray crystallography, the conformational properties of peptides 1-10 of β 3-aminoxy acids (NH 2OCHRCH 2COOH) having different side chains on the β carbon atom (e.g., R = Me, Et, COOBn, CH 2CH 2CH=CH 2, i-Bu, i-Pr). The β N-O turns and β N-O helices that involve a nine-membered-ring intramolecular hydrogen bond between NH 1+2 and CO 1, which have been found previously in peptides β 2,2-aminoxy acids (NH 2OCH 2CMe 2COOH), are also present in those β 3-aminoxy peptides. X-ray crystal structures and NMR spectral analysis reveal that, in the β N-O turns and β N-O helices induced by β 3-aminoxy acids, the N-O bond could be either anti or gauche to the C α-C β bond depending on the size of the side chain; in contrast, only the anti conformation was found in β 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 β N-O turn and β 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 β 3-aminoxy peptides.