Building proficient enzymes with foldamer prostheses.

Foldamers are non-natural oligomers that adopt stable conformations reminiscent of those found in proteins. To evaluate the potential of foldameric subunits for catalysis, semisynthetic enzymes containing foldamer fragments constructed from α- and ß-amino acid residues were designed and characterized. Systematic variation of the αâ†’ß substitution pattern and types of ß-residue afforded highly proficient hybrid catalysts, thus demonstrating the feasibility of expanding the enzyme-engineering toolkit with non-natural backbones.