Evidence that the β‐Peptide 14‐Helix is Stabilized by β3‐Residues with Side‐Chain Branching Adjacent to the β‐Carbon Atom

Abstract

AbstractOligomers 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 β‐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.