alpha-Peptide-Oligourea Chimeras: Stabilization of Short alpha-Helices by Non-Peptide Helical Foldamers

Short alpha-peptides with less than 10 residues generally display a low propensity to nucleate stable helical conformations. While various strategies to stabilize peptide helices have been previously reported, the ability of non-peptide helical foldamers to stabilize alpha-helices when fused to short alpha-peptide segments has not been investigated. Towards this end, structural investigations into a series of chimeric oligomers obtained by joining aliphatic oligoureas to the C- or N-termini of alpha-peptides are described. All chimeras were found to be fully helical, with as few as 2 (or 3) urea units sufficient to propagate an alpha-helical conformation in the fused peptide segment. The remarkable compatibility of alpha-peptides with oligoureas described here, along with the simplicity of the approach, highlights the potential of interfacing natural and non-peptide backbones as a means to further control the behavior of apeptides.