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

Amination and hydroxylation of the amide nitrogen in a peptide chain have little influence on the local geometry, but both affect the hydrogen-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 carried 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 chain. On the contrary, the N-hydroxyl group is a strong proton donor giving close contacts with the peptide carbonyls. The resulting folded conformers 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 simulation.