Synthesis and characterization of trans-2-aminocyclohexanecarboxylic acid oligomers: An unnatural helical secondary structure and implications for beta-peptide tertiary structure

The preperation, crystal structures, and circular dichroism(CD)spectra of t wo oligomers of optically active trans-2-aminocyclohexanecarboxylic acid ar e reported. In the solid state, both the tetramer and the hexamer of this b eta-amino acid display a helical conformation that involves 14-membered-rin g hydrogen bonds between a carbonyl oxygen and the amide proton of the seco nd residue toward the N-terminus. (For comparison, the familiar cc-helix ob served in conventional peptides is associated with a 13-membered-ring hydro gen, bond between a carbonyl oxygen and the amide proton of the fourth resi due toward the C-terminus.) These. :crystallographic data, along with CD da ta obtained in methanol, suggest that the 14-helix constitutes a stable sec ondary structure for beta-amino acid oligomers ("beta-peptides"). In additi on, the cryst al packing pattern observed for the hexamer offers a blueprin t for the design of beta-peptides that might adopt a helical bundle tertiar y structure.