Preferred Conformations of Azaamino Acids

Abstract

Azaamino acids are formed by the replacement of the α-carbon of amino acids with a nitrogen atom. They contain no extra functional group(s) unlike other constrained amino acids, and we believe that the azaamino acid is highly constrained because the Nα-C(O) bond has a double bond character in the urea-type structure. Moreover, when the azaamino acid is incorporated into peptides, the N-Nα bond of azaamino acids is between amide and urea. Since the amide and urea are quite planar, rotation of this bond is restrained. Thus, azaamino acids in peptides have unique conformational preference and their preferred (o, ψ) torsion angles are different from natural amino acids. In spite of wide usage and interesting conformational characteristics of azaamino acids, their conformational studies have not been extensively carried out. Aubry, Boussard and Marraud have made major contributions to this area carrying out crystal-lographic and spectroscopic studies. We also have studied the conformational preference of azaamino acids using computational methods and NMR spectroscopy. In this paper, we report the results of ab initio studies of model peptides containing 6 representative azaamino acids: Ac-AzGly-NHMe (acetyl azaglycine-N-methylamide), Ac-AzAla-NHMe (acetyl azaalanine-N-methylamide), Ac-AzLeu-NHMe (acetyl aza-leucine-N-methylamide), Ac-AzPhe-NHMe (acetyl azaphenylalanine-N-methylamide), Ac-AzAsn-NHMe (acetyl azaasparagine-N-methylamide) and Ac-AzPro-NHMe (acetyl azaproline-N-methylamide).