Synthetic Mimics of Serine Proteases via Covalent Imprinting of Photo‐Protected Template Molecules for Aryl Amide Hydrolysis

The rational design of enzyme-mimicking catalysts remains in its early stages. Beyond the controversies surrounding the origin of the catalytic efficiency found in enzyme catalysis, a large challenge lies in the synthetic construction of multifunctional active sites with precisely positioned binding and catalytic groups. Here, we present a rational strategy to create serine protease-mimicking molecularly imprinted nanoparticles (MINPs) via covalent imprinting within cross-linkable micelles, followed by photo-deprotection of the polymerized template molecules. Unlike previously reported protease mimics that work on activated ester substrates, the MINP-based catalysts are able to hydrolyze aryl amides under mild conditions. In addition, substrate selectivity can be finely tuned through the modular design of the template molecules.