Discrete Hf<sub>18</sub> Metal‐oxo Cluster as a Heterogeneous Nanozyme for Site‐Specific Proteolysis
Jens Moons, Francisco de Azambuja, Jelena Mihailović, Károly Kozma, Katarina Smiljanić, Mehran Amiri, Tanja Ćirković Veličković, May Nyman, Tatjana N. Parac‐Vogt
Abstract
Abstract The selective hydrolysis of proteins by non‐enzymatic catalysis is difficult to achieve, yet it is crucial for applications in biotechnology and proteomics. Herein, we report that discrete hafnium metal‐oxo cluster [Hf 18 O 10 (OH) 26 (SO 4 ) 13 ⋅(H 2 O) 33 ] ( Hf 18 ), which is centred by the same hexamer motif found in many MOFs, acts as a heterogeneous catalyst for the efficient hydrolysis of horse heart myoglobin (HHM) in low buffer concentrations. Among 154 amino acids present in the sequence of HHM, strictly selective cleavage at only 6 solvent accessible aspartate residues was observed. Mechanistic experiments suggest that the hydrolytic activity is likely derived from the actuation of Hf IV Lewis acidic sites and the Brønsted acidic surface of Hf 18 . X‐ray scattering and ESI‐MS revealed that Hf 18 is completely insoluble in these conditions, confirming the HHM hydrolysis is caused by a heterogeneous reaction of the solid Hf 18 cluster, and not from smaller, soluble Hf species that could leach into solution.