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

Abstract

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.

Keywords

• crosslinks
• dityrosine
• hydrolase activity
• peptide assemblies
• peptide nanostructures
• tyrosine