Is the Backbone Conformation of C~α-Methyl Proline Restricted to a Single Region?

摘要

C~α-Methyl-l-proline, or l-(aMe)Pro, is probably the most conformationally constrained α-amino acid. In particular, its ω and φ torsion angles are restricted to about 180 and -60°, respectively, and only three ranges of values are theoretically available for ψ in mono- or longer peptides, namely, about -30° (cis’, 3_(10)/α-helical structure), 60° (inverse γ turn), or 140° (trans’, poly(l-Pro)_n II structure). In this work, we examined the tendency of a number of N~α-acyl dipeptide N’-alkylamides of the type RCO-(αMe)Pro- Xxx-NHR’ or RCO-Xxx-(αMe)Pro- NHR’, in which Xxx is l (or d)-Ala, Aib (a-aminoisoburyric acid), or l (or d)-(αMe)Pro, long enough to fold into intramolecularly hydrogen-bonded γ or β turns. The results are compared with those obtained for the corresponding dipeptides based on Pro, a well-known turn-forming residue. For the crystalstate 3D-structural analysis we used Xray diffraction, whereas our solution conformational analysis was heavily based on the FTIR absorption and ~1H and ~(13)C NMR spectroscopy techniques. We conclude that (aMe)Pro is able to explore both trans’ and cis’ ψ areas of the conformational space, but in (αMe)Pro the latter is overwhelmingly more populated, in marked contrast to the Pro preference. This finding is a clear indication that in (αMe)Pro the major 3D-structural determinant is the C~α-methyl group. The circular dichroism (CD) signature of a peptide type III’ β-turn conformation is also proposed.