BETA-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-methanop henylalanine), have been studied in solution by using H-1 NMR and FT-I R spectroscopy and in the solid state by using X-ray diffraction. The conformational behavior of these compounds has been compared to that o f the analogous Ac(3)c and L- or D-Phe-containing dipeptides. When ass ociated to proline, the cyclopropane residues in the so-called i + 2 p osition 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, s olution, or solid state) and on the chirality of the c(3)Phe moiety, w hich 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 w ith the chi(1) angle constrained to about 0 degrees, is the most propi tious to beta I-folding in the i + 2 position of a putative beta-turn.