Effect of side chains on turns and helices in peptides of beta(3)-aminoxy acids

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 (NH2OCHRCH2COOH) having different side chains on the beta carbon atom (e.g., R = Me, Et, COOBn, CH2CH2CH=CH2, i-Bu, i-Pr). The beta N-O turns and beta N-O helices that involve a nine-membered-ring intramolecular hydrogen bond between NHi+2 and COj, which have been found previously in peptides of beta(2,2)-aminoxy acids (NH2OCH2CMe2COOH), 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.