Relationship between side-chain branching and stoichiometry in β3-peptide bundles

The stability and stoichiometry of β3-peptide bundles is influenced by side-chain identity. Previously reported β3-peptides containing β3-homoleucine on one helical face assemble into octamers, whereas those containing β3-homovaline form tetramers. The side chains of β3-homoleucine and β3-homovaline differ in terms of both side-chain length and γ-carbon branching. To evaluate the extent to which these two parameters control β3-peptide bundle stoichiometry, we synthesized the β3-peptide Acid-3Y, which contains β3-homoisoleucine in place of β3-homoleucine or β3-homovaline on one helical face. Acid-3Y assembles into a stable tetramer whose stability resembles that of the previously characterized Acid-VY tetramer. These results suggest that β3-peptide bundle stoichiometry can be modulated by the presence or absence of γ-carbon branching on core side chains.