Helix Bundle Quaternary Structure from α/β-Peptide Foldamers

The function of a protein generally depends on adoption of a specific folding pattern, which in turn is determined by the side chain sequence along the polypeptide backbone. Here we show that the sequence-encoded structural information in peptides derived from yeast transcriptional activator GCN4 can be used to prepare hybrid α/β-peptide foldamers that adopt helix bundle quaternary structures. Crystal structures of two hybrid α/β-peptides are reported along with detailed structural comparison to α-peptides of analogous side chain sequence. There is considerable homology between α- and α/β-peptides at the level of helical secondary structure, with modest but significant differences in the association geometry of helices in the quaternary structure.