Zirconium-based MOF and metal-oxo clusters were demonstrated to mediate backbone cleavage of proteins through their Lewis acidic actions (Scheme 17B, 17C). Parac-Vogt and co-workers introduced a zirconium(IV)-based MOF as a heterogeneous catalyst for proteolysis of model protein substrates. The hydrolysis was proposed to proceed through the activation of the amide backbones by Lewis acidic Zr(IV) centers incorporated in the MOF catalyst. Hexazirconium metaloxo cluster was a building block of the specific MOF catalyst, which was assembled by capping and interconnection by six benzene-1,3,5-tricarboxylate linker in a trigonal antiprism fashion. The water-soluble metal-oxo cluster, [Zr6O4(OH)4(CH3CO2)8(H2O)2Cl3] + showed superior hydrolytic activity compared to the zirconium MOF catalyst. 268 Some metaloxo cluster-based catalysts (e.g., cerium-based polyoxometalate 269 and molybdenum-based polyoxometalate 270 ) showed unique properties such as regioselectivity potentially arising from the enzyme-like non-covalent interaction with specific regions of proteins. Another explanation for such enzymatic behaviors is that the catalysts might make cleavage sites more accessible through partial unfolding of protein structures of proteins. As the hexazirconium metal-oxo cluster is a component of the MOFs, 268 the metal-oxo cluster component has been used for mechanistic studies showing the accessibility of the catalyst active site by protein substrates and its similarity of the catalytic action to the hafnium cluster as described below.