Ambidextrous molecules: Cylindrical peptide structures formed by fusing left- and right-handed helices

Abstract

The handedness or chirality of molecules, organisms, and elementary particles has been widely appreciated, vindicating Pasteur’s perceptive generalization, Luni-vers est dissymktrique. Ambidexterity is rare not only in biological organisms but also in molecules. One of the most striking chiral features in biopolymers is the twist or handedness of the helices that are frequently formed. Cylindrical helical structures formed by polypeptide chains are an important constituent of peptide and protein structure, The most widespread helical structures are the alpha-helix and 310-helix, both of which have a right-handed screw sense in proteins, determined by the L configuration of the component amino acids. Peptide sequences with alternating L and D residues occur in the membrane channel-forming I 5-residue peptide gramicidin A, resulting in a large diameter cylindrical structure formed by wrapping beta strands about the helix axis.’ Alternating L,D sequences in cyclic peptides have yielded novel tubular stack. Helical polymers with alternating left- and right-handed blocks have been studies in polyisocyanates, providing new insights into the effect of chiral biases on polymer properties. In order to develop novel synthetic structures using chiral blocks, we have investigated peptides with strong helix-forming tendencies generated so as to fuse left- and right-handed cylindrical screws in the same molecule. We describe below the structural characterization of a 14-residue hydrophobic peptide containing two heptapeptide blocks of opposite chirality.