Structural Mimicry of the α-Helix in Aqueous Solution with an Isoatomic α/β/γ-Peptide Backbone

Artificial mimicry of alpha-helices offers a basis for development of protein-protein interaction antagonists. Here we report a new type of unnatural peptidic backbone, containing alpha-, beta-, and gamma-amino acid residues in an alpha gamma alpha alpha beta alpha repeat pattern, for this purpose. This unnatural hexad has the same number of backbone atoms as a heptad of alpha residues. Two-dimensional NMR data clearly establish the formation of an alpha-helix-like conformation in aqueous solution. The helix formed by our 12-mer alpha/beta/gamma-peptide is considerably more stable than the alpha-helix formed by an analogous 14-mer alpha-peptide, presumably because of the preorganized beta and gamma residues employed.