On the Ability of Modified Peptide Links to Form Hydrogen Bonds

The hydrogen-bonding capabilities of modified amide groups have been investigated by theoretical methods. More specifically, the groups considered in this work are retroamide, N-hydroxamide, N-amino amide, and thioamide, which are usually employed to design pseudopeptides. Ab initio calculations with inclusion of correlation effects at the Møller−Plesset level have been used to characterize complexes containing the interaction between a standard amide group and a modified amide group. Furthermore, self-consistent reaction-field calculations have been performed to analyze the effects of the aqueous solvent on these complexes. The results allow rationalization of the changes induced in the hydrogen-bonding network by modification of the amide bond.