The development of novel beta-peptide foldamers: 1. Tertiary amide beta-peptide oligomers. 2. Chimeric alpha/beta-peptide hairpins

Beta-peptides, a class of foldamers, have been developed that mimic the major types of secondary structure (helices, hairpins, and reverse turns) found in Nature. The continual search for novel types of beta-peptide secondary structure is an important endeavor. The research presented in this thesis is a compilation of efforts toward that goal. Two major avenues were explored in the search for novel secondary structures that incorporate beta-amino acids: tertiary amide beta-peptides and chimeric alpha/beta-peptides.; Tertiary amide beta-peptides have been developed that were intended to loosely mimic polyproline helices found in Nature. Carbon-13 and two-dimensional NMR spectroscopy suggest that beta-peptides composed of 5,5-geminally disubstituted pyrrolidine-3-carboxylic acid residues adopt a conformationally rigid, regularly repeating secondary structure.; A chimeric hairpin was designed that incorporated two different classes of secondary structure: an alpha-peptide strand and a beta-peptide reverse turn. This discovery sparked the synthesis of a Ribonuclease A analog that incorporated the beta-peptide reverse turn, which was shown to be as stable and active as the native enzyme.