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.