The homologous RCO-Pro-Xaa-NHR‘ model pseudodipeptides containing the reduced peptide (CαCH2NHCα), reduced azapeptide (CαCH2NHNα), methyleneoxy (CαCH2OCα), and iminoazapeptide (CαCHNNα) surrogate of the middle amide group have been prepared. Their structural analysis has been carried out
in solution by 1H NMR and IR spectroscopy and in the solid state by X-ray diffraction. The last three fragments,
not protonated in the pH range 2−12, and the reduced fragment in its neutral amine form induce quite similar
molecular structures characterized by a hydrogen bond between NHR‘ and the N/O atom replacing the amide
NH group and closing a five-membered cycle. The neutral amine or protonated ammonium state of the reduced
amide fragment, with a pK
a value of about 7, depends on the environment. Protonation induces a conformational
transition due to the strong proton donating properties of the ammonium group which interacts with the RCO
carbonyl.
Reduced dipeptides with the general formula RCO-Xaa-rXbb-N+HR'R" (rXbb, reduced analogue of residue Xbb: NH-C alpha HR1-CrH2) are shown to adopt a folded conformation in solution and in the solid state. The protonated reduced amide bond is an active proton donor capable of interacting with a peptide carbonyl to give a strong hydrogen bond topologically equivalent to the i+2 or i+3-->i interaction. The resulting conformation is similar to the y- or beta-turn structure found in peptides and proteins.
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