Exploring a β-Amino Acid with a Seven-Membered Ring Constraint as a Foldamer Building Block for Nontraditional Helices

We explored trans - and cis -2-aminocycloheptanecarboxylic acid (ACHpC) as potential building blocks for helical foldamers. trans -ACHpC does not show sufficient folding propensity in unnatural peptides. cis -ACHpC promotes nontraditional helices of two unnatural peptide backbones: the 11/9-helix for 1:1 α/β-peptides and the 12/10-helix for β-peptides with interconvertible handedness. The two opposite-handed 12/10-helices rapidly interconvert in solution by pseudorotation of the two twist chair forms of the cycloheptane moiety in each cis -ACHpC residue.