Heterogeneous catalysts could be beneficial for proteolysis applications due to their tunable properties and facile separation from products (Scheme 17A). One of the earliest documented heterogeneous catalysis is Faraday's oxidation reactions by platinum catalysts in the 1800s. The advantages of heterogeneous catalysts are reusability and easier separation of catalysts. While there are many heterogeneous catalytic systems for small molecule substrates, catalysts that can be applicable for protein substrates are quite scarce. As described in the following paragraphs, metal-organic framework (MOF)based platforms are one of the few examples that act as heterogeneous catalysis for protein substrates. MOFs are crystalline materials composed of metal ions and organic ligands. Properties of MOFs such as pore size, type of metal ions, and surface area are tunable. As described in the acid catalyst section, artificial proteases composed of non-biomolecule building blocks could be useful for the digestion of proteins because of unique cleavage sites of such approaches. While MOF catalysts are also useful for the same purposes (i.e., hydrolysis of the protein backbones), the protein-hosting ability of MOFs can be an additional advantage for the following two reasons: 260 (1) The space confinement effect of MOF mesopores could mimic enzymes active site, as demonstrated in a few reports. (2) The heterogeneous nature of MOFs can be advantageous for proteomics digestion purposes, as the catalysts can easily be separated from products after the reaction. As free metal ions could also be a catalyst for given reaction systems, 200 it is often important that a MOF catalyst possesses chemical and structural stability, so that fragments/components of MOF through decomposition would not induce unwanted processes. For instance, one of the early reports for MOF-catalyzed proteolysis described leaching of Cu(II) ions from the MOF, 260 although the Cu(II) ion was not ascribed to the catalytic activity of the system.