β-turn preferences induced by 2,3-methanophenylalanine chirality

The model dipeptides RCO-L-Pro-c(3)Phe-NHMe, where c(3)Phe stands for each of the four cyclopropane analogues of phenylalanine (2,3-methanophenylalanine), have been studied in solution by using H-1 NMR and FT-IR spectroscopy and in the solid state by using X-ray diffraction. The conformational behavior of these compounds has been compared to that of the analogous Ac(3)c and L- or D-Phe-containing dipeptides. When associated to proline, the cyclopropane residues in the so-called i + 2 position exhibit a marked tendency to beta-folding in solution, even in DMSO. The type II beta-turn is generally favored, but the beta I/beta II-turn ratio depends both on the experimental conditions (solvent, solution, or solid state) and on the chirality of the c(3)Phe moiety, which rigidly fixes the orientation of the phenyl ring with respect to the peptide backbone. The (2S,3S)c(3)Phe residue, analogous to L-Phe with the chi(1) angle constrained to about 0 degrees, is the most propitious to beta I-folding in the i + 2 position of a putative beta-turn.