Artificial amidase with modifiable active sites and designable substrate selectivity for aryl amide hydrolysis.

Abstract

Hydrolases are used by cells to process key biomolecules including peptides and esters. Previous synthetic mimics of proteases generally only hydrolyze highly active ester derivatives. We report a synthetic catalyst with an acid/base dyad in its active site that hydrolyzes aryl amides under near physiological conditions. The aspartic protease mimic achieves substrate selectivity by its imprinted active site, which is tunable through different template molecules used during molecular imprinting. It can be designed to maintain or override the intrinsic activities of aryl amides in a predictable manner.