N-METHYL PEPTIDES .9. INFLUENCE ON THE ORIENTATION OF THE SIDE-SUBSTITUENTS

The influence of N-methylation on the preferential orientations of the peptide side-substituents has been studied on Pro-X and X-Pro sequences (X = Ala, Leu or Phe), protected on both ends by amide functions. We have considered the vicinal coupling constants in the Cα H-Cβ H2 fragment and the upfield shifts of the Pro proton signals due to the Phe phenyl ring, on the basis of the conformations assumed by the peptide backbone. It appears that N-methylation does not affect the Cα-Cβ rotamer distribution for leucine, but greatly destabilizes the g- g+ conformation for phenylalanine In the latter case, the release of an attractive interaction between Phe-NH and π-orbitals, due to N-methylation. must also be considered.