Conformational Preference of Acetyl-Azaalanine-N-Methyl Amide

Abstract

Conformational preference of Ac-AzAla-NHMe has been investigated using ab initio calculations. Azaalanine in peptides prefer to adopt two conformational families including four conformations in which (φ,ψ) are (-90°, -13°), (90°, 13°), (-70°, 164°) and (70°, -164°). The stability at φ = ±90° is explained by repulsion of lone pairs on the nitrogens and hydrogen bonding between Ac-N and terminal N(Me)H. On the other hand, the angle ψ adopts only ~0° or 180° since the N(Me)-C(O) bond has double bond character. One conformational family in which the (φ,ψ) torsion angles are (-90°, -13°) or (90°, 13°), is similar to the i+2 position of typical β-I or β-II turns. The other conformation in which the (φ,ψ) torsion angles are (-70°, 164°) or (70°, -164°), is similar to the polyproline II structure appearing in collagen. We believe that these results are useful in designing constrained peptidomimetics for drug discovery and peptide engineering.