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 1 H 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 β-folding in solution, even in DMSO. The type II β-turn is generally favored, but the βI/βII-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 (2 S,3 S )c 3 Phe residue, analogous to l -Phe with the χ 1 angle constrained to about 0°, is the most propitious to βI-folding in the i + 2 position of a putative β-turn.