STRUCTURAL COMPARISON OF HOMOLOGOUS REDUCED PEPTIDE, REDUCED AZAPEPTIDE, IMINOAZAPEPTIDE, AND METHYLENEOXYPEPTIDE ANALOGS

The homologous RCO-Pro-Xaa-NHR' model pseudodipeptides containing the reduced peptide ((CCH2NHCalpha)-C-alpha), reduced azapeptide ((CCH2NHN alpha)-C-alpha), methyleneoxy ((CCH2OCalpha)-C-alpha), and iminoazapep tide ((CCH)-C-alpha=NNalpha) surrogate of the middle amide group have been prepared. Their structural analysis has been carried out in solut ion by H-1 NMR and IR spectroscopy and in the solid state by X-ray dif fraction. The last three fragments, not protonated in the pH range 2-1 2, and the reduced fragment in its neutral amine form induce quite sim ilar molecular structures characterized by a hydrogen bond between NHR ' and the N/O atom replacing the amide NH group and closing a five-mem bered cycle. The neutral amine or protonated ammonium state of the red uced amide fragment, with a pK(a) value of about 7, depends on the env ironment. Protonation induces a conformational transition due to the s trong proton donating properties of the ammonium group which interacts with the RCO carbonyl.