The effect of backbone stereochemistry on the folding of acyclic β2,3-aminoxy peptides

Abstract

As a new type of foldamer, β-aminoxy peptides have the ability to adopt novel β N-O turns or β N-O helices in solution. Herein, we describe a new subclass of β-aminoxy peptide, that is, peptides of acyclic β2,3-aminoxy acids (NH2OCHR1CHR 2COOH), in which the presence of two chiral centers provides insight into the effect of backbone stereochemistry on the folding of β-aminoxy peptides. Acyclic β2,3aminoxy peptides with syn and anti configurations have been synthesized and their conformations investigated by NMR, IR, and circular dichroism (CD) spectroscopic, and X-ray crystallographic analysis. The ß N-O turns or β N-O helices, which feature ninemembered rings with intramolecular hydrogen bonds and have been identified previously in peptides of β3- and β2,2-aminoxy acids, are also predominantly present in the acyclic β2,3- aminoxy peptides with a syn configuration and N-O bonds gauche to the C a-Cβ bonds in both solution and the solid state. In the acyclic β2,3-aminoxy peptides with an anti configuration, an extended strand (i.e., non-hydrogenbonded state) is found in the solid state, and several conformations including non-hydrogen-bonded and intramolecular hydrogen-bonded states are present simultaneously in nonpolar solvents. These results suggest that the backbone stereochemistry does affect the folding of the acyclic β2,3-aminoxy peptides. Theoretical calculations on the conformations of model acyclic β2,3-aminoxy peptides with different backbone stereochemistry were also conducted to elucidate structural characteristics. Our present work may provide useful guidelines for the design and construction of new foldamers with predicable structures. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.