Hydrazino peptides as foldamers: an extension of the beta-peptide concept.

Abstract

Replacing the C(beta) atoms in the beta-amino acid constituents of beta-peptides by nitrogen atoms leads to hydrazino peptides. A systematic conformation analysis of blocked hydrazino peptide oligomers of the general type I at the HF/6-31G, MP2/6-31G, and DFT/B3LYP/6-31G levels of ab initio MO theory and on the basis of molecular mechanics reveals a wide variety of secondary structures, as for instance various helices and sheet- and turnlike conformers. Some of them are closely related to secondary structure types found in beta-peptides; others represent novel types. Thus, a very stable, novel helix with 14-membered hydrogen-bonded pseudocycles, which occupies a conformation space different from that of helices with 14-membered rings found among the most stable conformers in beta-peptides, is indicated. The most important secondary structure elements are characterized by interactions between peptidic NH and CO groups. The additional hydrazino N(alpha)H group takes part in special structuring effects but is of lesser importance for secondary structure formation. The influence of environmental effects on the existence and stability of the various structure types is discussed. Due to the wide variety of structural possibilities, hydrazino peptides might be a useful tool for peptide and protein design.