Controlling the Helix Handedness of ααß-Peptide Foldamers through Sequence Shifting.

Peptide foldamers containing both cis-ß-aminocyclopentanecarboxylic acid and α-amino acid residues combined in various sequence patterns (ααß, αααß, αßααß, and ααßαααß) were screened using CD and NMR spectroscopy for the tendency to form helices. ααß-Peptides were found to fold into an unprecedented and well-defined 16/17/15/18/14/17-helix. By extending the length of the sequence or shifting a fragment of the sequence from one terminus to another in ααß-peptides, the balance between left-handed and right-handed helix populations present in the solution can be controlled. Engineering of the peptide sequence could lead to compounds with either a strong propensity for the selected helix sense or a mixture of helical conformations of opposite senses.