CuCoO2 Nanoparticles as a Nanoprotease for Selective Proteolysis with High Efficiency at Room Temperature

Abstract Many nanoproteases contain tetravalent metal ions and catalyze peptide‐bond hydrolysis only at high temperature (60 °C). Here, we report a new and effective strategy to explore nanoproteases from nanoparticles containing low valent metal ions. We found that flower‐like CuCoO 2 nanoparticles (CuCoO 2 NPs) containing low valent Cu + possessed excellent catalytic activity towards selective cleavage of peptide bonds with hydrophobic residues in bovine serum albumin (BSA) at room temperature. CuCoO 2 NPs exhibited excellent stability and had great reusability. CuCoO 2 NPs also hydrolyzed heat‐denatured and surfactant‐denatured BSA. Mechanism analysis revealed that the high Lewis acidity of Co 3+ and the low valence of Cu + were both essential for the high protease activity of CuCoO 2 NPs. The flower‐like structure of CuCoO 2 NPs and the strong nucleophilicity of Cu + ‐bound hydroxyl endow them with excellent catalytic performance. The findings open a new way for the design and discovery of high‐efficiency nanoproteases.