An Enzyme Model Which Mimics Chymotrypsin and N-Terminal Hydrolases
José J. Garrido‐González, Ma Mercedes Iglesias Aparicio, Miguel Martínez García, Luis Simón, Francisca Sanz, Joaquı́n R. Morán, Ángel L. Fuentes de Arriba
Abstract
Enzymes are the most efficient and specific catalysts to date. Although they have been thoroughly studied for years, building a true enzyme mimic remains a challenging and necessary task. Here, we show how a three-dimensional geometry analysis of the key catalytic residues in natural hydrolases has been exploited to design and synthesize small-molecule artificial enzymes which mimic the active centers of chymotrypsin and N-terminal hydrolases. The optimized prototype catalyzes the methanolysis of the acyl enzyme mimic with a half-life of only 3.7 min at 20 °C, and it is also able to perform the transesterification of vinyl acetate at room temperature. DFT studies and X-ray diffraction analysis of the catalyst bound to a transition state analogue proves the similarity with the geometry of natural hydrolases.