First β-Hairpin β-Helix Peptide

An unprecedented peptide structure–a cyclic β-hairpin β-helix (shown, with side chains)–has been designed, synthesized, and characterized by Thomas D. Clark and Christopher Brown of the Naval Research Laboratory, Washington, D.C.; and Mallika Sastry and Gerhard Wagner of Harvard Medical School (J. Am. Chem. Soc., DOI: 10.1021/ja062737f).

β-Helices are formed by peptides composed of alternating D- and L-amino acids and are stabilized by β-sheet-type hydrogen bonding. The antibiotic gramicidin A is a naturally occurring β-helical peptide, and several attempts have been made to synthesize similar structures, but previous efforts resulted in single- and double-stranded helical mixtures.

Now, Clark and coworkers have solved that problem by tying together two appropriate peptide strands into a cyclic structure with β-hairpin ends. Such β-hairpin β-helices could serve "as structural templates for a variety of potential applications in bioorganic chemistry, from new transmembrane ion channels, to new ligands for macromolecular targets such as DNA, to building blocks for new protein architectures," Clark says.