Residue-based control of helix shape in β-peptide oligomers

Proteins and RNA are unique among known polymers in their ability to adopt compact and well-defined folding patterns. These two biopolymers can perform complex chemical operations such as catalysis and highly selective recognition, and these functions are linked to folding in that the creation of an active site requires proper juxtaposition of reactive groups. So the development of new types of polymeric backbones with well-defined and predictable folding propensities ('foldamers') might lead to molecules with useful functions1,2. The first step in foldamer development is to identify synthetic oligomers with specific secondary structural preferences3–13. Whereas α-amino acids can adopt the well-known α-helical motif of proteins, it was shown recently11–13 that β-peptides3 constructed from carefully chosen β-amino acids can adopt a different, stable helical conformation defined by interwoven 14-membered-ring hydrogen bonds (a 14-helix; Fig. la). Here we report that β-amino acids can also be used to design β-peptides with a very different secondary structure, a 12-helix (Fig. la). This demonstrates that by altering the nature of β-peptide residues, one can exert rational control over the secondary structure.