12/14/14-Helix Formation in 2:1 α/ß-Hybrid Peptides Containing Bicyclo[2.2.2]octane Ring Constraints.

ABSTRACT

The highly constrained ß-amino acid ABOC induces different types of helices in ß urea and 11 α/ß amide oligomers. The latter can adopt 11/9- and 18/16-helical folds depending on the chain length in solution. Short peptides alternating proteinogenic α-amino acids and ABOC in a 21 α/ß repeat pattern adopted an unprecedented and stable 12/14/14-helix. The structure was established through extensive NMR, molecular dynamics, and IR studies. While the 11 α-AA/ABOC helices diverged from the canonical α-helix, the helix formed by the 9-mer 21 α/ß-peptide allowed the projection of the α-amino acid side chains in a spatial arrangement according to the α-helix. Such a finding constitutes an important step toward the conception of functional tools that use the ABOC residue as a potent helix inducer for biological applications.