Evidence that the <i>β</i>‐Peptide <i>14</i>‐Helix is Stabilized by <i>β</i>³‐Residues with Side‐Chain Branching Adjacent to the <i>β</i>‐Carbon Atom

Abstract

Abstract Oligomers of β ‐substituted β ‐amino acids (‘ β 3 ‐peptides') are known to adopt a helical secondary structure defined by 14‐membered ring hydrogen bonds (' 14 ‐helix'). Here, we describe a deca‐ β 3 ‐peptide, 1 , that does not adopt the 14 ‐helical conformation and that may prefer an alternative secondary structure. β 3 ‐Peptide 1 is composed exclusively of residues with side chains that are not branched adjacent to the β ‐C‐atom ( β 3 ‐hLeu, β 3 ‐hLys, and β 3 ‐hTyr). In contrast, an analogous β ‐peptide, 2 , containing β 3 ‐hVal residues in place of the β 3 ‐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 β 3 ‐peptides.