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

Oligomers of beta-substituted beta-amino acids ('beta(2)-peptides') are known to adopt a helical secondary structure defined by 14-membered ring hydrogen bonds ('14-helix'). Here we describe a deca-beta(2)-peptide. 1. that does not adopt the 14-helical conformation and that may prefer an alternative secondary structure, beta(2)-Peptide 1 is composed exclusively of residues with side chains that are not branched adjacent to the beta-C-atom (beta(2)-hLeu. beta(2)hLys. and beta(2)-hTyr). In contrast. an analogous beta-peptide, 2. containing residues in place of the beta(2)-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 beta(2)-peptides.