Conformational preference of acetyl-azaalanine-N-methyl amide

Conformational preference of Ac-AzAla-NHMe has been investigated using ab i nitio calculations. Azaalanine in peptides prefer to adopt two conformation al families including four conformations in which (phi, psi) are (-90 degre es, -13 degrees), (90 degrees, 13 degrees), (-70 degrees, 164 degrees) and (70 degrees, -164 degrees). The stability at phi = +/- 90 degrees is explai ned by repulsion of lone pairs on the nitrogens and hydrogen bonding betwee n Ac-N and terminal N(Me)H. On the other hand, the angle psi adopts only si milar to0 degrees or 180 degrees since the N(Me)-C(O) bond has double bond character. One conformational family in which the (phi, psi) torsion angles are (-90 degrees, -13 degrees) or (90 degrees, 13 degrees), is similar to the i + 2 position of typical beta -I or beta -II turns. The other conforma tion in which the (phi, psi) torsion angles are (-70 degrees, 164 degrees) or (70 degrees, -164 degrees), is similar to the polyproline II structure a ppealing in collagen. We believe that these results are useful in designing constrained peptidomimetics for drug discovery and peptide engineering.