RESIDUE-BASED CONTROL OF HELIX SHAPE IN BETA-PEPTIDE OLIGOMERS

Proteins and RNA are unique among known polymers in their ability to a dopt compact and well-defined folding patterns. These two biopolymers can perform complex chemical operations such as catalysis and highly s elective recognition, and these functions are linked to folding in tha t the creation of an active site requires proper juxtaposition of reac tive groups. So the development of new types of polymeric backbones wi th well-defined and predictable folding propensities ('foldamers') mig ht lead to molecules with useful functions(1,2). The first step in fol damer development is to identify synthetic oligomers with specific sec ondary structural preferences(3-13). Whereas alpha-amino acids can ado pt the well-known alpha-helical motif of proteins, it was shown recent ly(11-13) that beta-peptides(3) constructed from carefully chosen beta -amino acids can adopt a different, stable helical conformation define d by interwoven 14-membered-ring hydrogen bonds (a 14-helix; Fig. 1a). Here we report that beta-amino acids can also be used to design beta- peptides with a very different secondary structure, a 12-helix (Fig. 1 a). This demonstrates that by altering the nature of beta-peptide resi dues, one can exert rational control over the secondary structure.