Covalently Self‐Assembled Peptide‐Based Hydrolase Mimic for Realizing Exceptional Catalytic Longevity in Foreign Environments

As a de novo design of artificial enzymes, peptide assembly is receiving enormous attention. However, the development of durable peptide-based biocatalysts that can resist undesirable deformation and loss of function in non-native environments is challenging. Herein, a covalently self-assembled, peptide-based hydrolase mimic (referred to as a nanopepzyme) with exceptional stability regardless of the changes in the external environment is reported. The photocrosslinking of decapeptides, YYHHHHHHYY, leads to the formation of well-defined nanospheres with multiple catalytic histidine residues protruding from their surfaces. The nanopepzyme not only exhibits extraordinary long-term stability even after 6 months but also maintains its structures under adverse environmental conditions (pH, temperature, ion strength, and organic solvents). In addition, the nanopepzyme demonstrates hydrolase-like activity and is effective as a significantly durable biocatalyst, as verified by the model reactions following incubation under various harsh conditions. This study expands the scope of peptide assembly for the preparation of peptide-based biocatalysts that can be applied in considerably harsh foreign environments.