Journal of the American Chemical Society 2011-05-18

Structural mimicry of the α-helix in aqueous solution with an isoatomic α/β/γ-peptide backbone.

Tomohisa Sawada, Samuel H Gellman

Index: J. Am. Chem. Soc. 133 , 7336-7339, (2011)

Full Text: HTML

Abstract

Artificial mimicry of α-helices offers a basis for development of protein-protein interaction antagonists. Here we report a new type of unnatural peptidic backbone, containing α-, β-, and γ-amino acid residues in an αγααβα repeat pattern, for this purpose. This unnatural hexad has the same number of backbone atoms as a heptad of α residues. Two-dimensional NMR data clearly establish the formation of an α-helix-like conformation in aqueous solution. The helix formed by our 12-mer α/β/γ-peptide is considerably more stable than the α-helix formed by an analogous 14-mer α-peptide, presumably because of the preorganized β and γ residues employed.© 2011 American Chemical Society