Evidence that the β-peptide 14-helix is stabilized by β³-residues with side-chain branching adjacent to the β-carbon atom

Oligomers of β-substituted β-amino acids ('β³-peptides') are known to adopt a helical secondary structure defined by 14-membered ring hydrogen bonds ('14-helix'). Here, we describe a deca-β³-peptide, 1, that does not adopt the 14-helical conformation and that may prefer an alternative secondary structure, β³-Peptide 1 is composed exclusively of residues with side chains that are not branched adjacent to the β-C-atom β³-hLeu, β³-hLys, and β³-hTyr). In contrast, an analogous β³-peptide, 2, containing β³-hVal residues in place of the β³-hLeu residues of 1, adopts a 14-helical conformation in MeOH, according to CD data. These results illustrate the importance of side-chain branching in determining the conformational preferences of β³-peptides.