CONFORMATIONAL PERTURBATIONS INDUCED BY N-AMINATION AND N-HYDROXYLATION OF PEPTIDES

Amination and hydroxylation of the amide nitrogen in a peptide chain h ave little influence on the local geometry, but both affect the hydrog en-bonding network, and therefore the conformational properties of the modified peptide. An experimental study in solution (IR spectroscopy and H-1-NMR) and in the solid state (X-ray diffraction) has been carri ed out on the N-amino and N-hydroxy analogues of the two RCO-Pro-NHMe and RCO-Pro-Gly-NHiPr peptides known to adopt preferentially the gamma - and beta-turn structures, respectively. The N-amino group is a weak proton donor which does not interact significantly with the peptide ch ain. On the contrary, the N-hydroxyl group is a strong proton donor gi ving close contacts with the peptide carbonyls. The resulting folded c onformers of an expanded gamma- or beta-like type, presenting an 8- or 11-membered cycle instead of a 7- or 10-membered cycle in the cognate peptides have been also analyzed by a SYBYL molecular dynamics simula tion.