Promotion of 11/9-helical folding in α/β-peptides containing β²-homoalanine residue

The 11/9-helix is one of nontraditional helices available to α/β-peptides with alternating residue types. Several β-amino acid residues are known to promote 11/9-helical folding with two types of intramolecular hydrogen bonds. Both β²-amino acids and β³-amino acids are common acyclic β-amino acids that can be regarded as homologs of α-amino acids with the same side chain group. However, β²-amimo acids have not been widely used as much as β³-amino acids partly because β²-residue is believed to be not as strong as β³-residue in promoting a distinct conformation. Here we report 11/9-helical folding of α/β-peptides that consist of L-α-alanine and (S)-β²-homoalanine with residue alternation. In addition, circular dichroism study reveals that β²-homoalanine promotes 11/9-helical folding more strongly than β³-homoalanine in polar protic solvent conditions.