Discrete Hf₁₈ Metal‐oxo Cluster as a Heterogeneous Nanozyme for Site‐Specific Proteolysis

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 [Hf18O10(OH)26(SO4)13⋅(H2O)33] (Hf18), 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 HfIV Lewis acidic sites and the Brønsted acidic surface of Hf18. X‐ray scattering and ESI‐MS revealed that Hf18 is completely insoluble in these conditions, confirming the HHM hydrolysis is caused by a heterogeneous reaction of the solid Hf18 cluster, and not from smaller, soluble Hf species that could leach into solution.

Interplay between structural parameters and reactivity of Zr6-based MOFs as artificial proteases

“…Several homogeneous articial metalloproteases have been reported over the years, but heterogeneous catalysts for the selective peptide bond cleavage are still largely underdeveloped. 14 During the past decade, we discovered and developed the unique hydrolytic activity of Zr(IV) substituted polyoxometalates (Zr IV -POMs) toward the selective cleavage of peptide bonds in short peptides and even proteins. [15][16][17][18][19][20][21][22][23] However, purication and/or analysis of protein digest, as well as catalyst recyclability were hampered by the solubility of Zr IV -POMs in water, precluding any practical applications.…”

Selective Hydrolysis of Transferrin Promoted by Zr-Substituted Polyoxometalates

“…In the last few years our research group has been developing a new class of artificial metalloproteases based on metal-oxo-based materials and on metal-substituted polyoxometalates, which are able to selectively hydrolyze proteins under mild experimental conditions while producing larger peptide fragments [ 9 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. Polyoxometalates are a large class of inorganic metal-oxygen clusters which are composed of transition metals in their highest oxidation state.…”

Metal Nanozymes: New Horizons in Cellular Homeostasis Regulation

“…The important qu in the research seems to consist not so much in proving the catalytic abilities of subseq metallic nanoparticles and metaloxides but in the use of a set of structural solutio experimental design (Figure 4). This brings particularly interesting effects that inspire approaches to nanozyme catalysis, allowing very selective activities of nanozymes, a the case in an interesting work of Parac-Vogt et al [76] on discrete hafnium meta cluster [Hf18O10(OH)26(SO4)13 • (H2O)33] (Hf18), centered by the hexamer motif found in MOFs. This water-insoluble nanoparticle acts as a heterogeneous catalyst for the eff hydrolysis of horse heart myoglobin (HHM), inducing a strictly selective cleavage rected protein sites.…”