12/10-Helical β‑Peptide with Dynamic Folding Propensity: Coexistence of Right- and Left-Handed Helices in an Enantiomeric Foldamer

We present the first examples of
atomic-resolution crystal data
for the β-peptide 12/10-helix from oligomers of cis-2-aminocyclohexane carboxylic acid (cis-ACHC) with
alternating chirality. The local conformations of two enantiomeric cis-ACHC dimer units suggested that a chiral β-peptide
may adopt both right-handed and left-handed helical conformations
in solution. To probe the conformational behavior of 12/10-helical
β-peptides, the two reference helices with a single handedness
were synthesized with a more rigidified cis-ACHC
derivative. Comparison with these reference helices at low temperature
revealed that a chiral cis-ACHC oligomer with alternating
chirality indeed displays 12/10-helical conformations with both handedness
that equilibrate rapidly in solution. This is a very rare example
of chiral oligomers with helix inversion ability. The 12/10-helical
backbone should be a valuable addition to potential scaffolds for
applications involving helices with dynamic folding propensity.