Abstract

Effective catalysts for the controlled transformation of large and complex biomolecules are rare and challenging to develop. In particular, selective hydrolysis of proteins by non-enzymatic catalysis is difficult to achieve, yet it is crucial for many modern applications in biotechnology and proteomics. In recent years we have discovered  the conceptually new way selectively cleaving proteins by combining the enzyme-like molecular recognition ability of a water-soluble polyoxometalate (POM) scaffolds with the hydrolytic activity of a strong Lewis acid metal cation imbedded into the POM structure. In our approach, the POM acts as a ligand for the Zr(IV) or Hf(IV) ion, and due to its three-dimensional shape and negative charge it also induces the selectivity that is necessary for a controlled fragmentation of the polypeptide backbone. A selective cleavage that occurs predominantly at Asp-X peptide bonds located at positive patches that are able to accommodate the POM ligand, has been demonstrated in a range of different proteins differing in three-dimensional structure, size and charge. More recently, we have shown that {Zr₆O₈} -based metal−organic frameworks act as very effective heterogeneous catalysts for the hydrolysis of the peptide bond in a wide range of peptides. The catalytic activity of MOF-808 was shown to be excellent through a broad pH range, resulting in the rate constants which are more than 4 orders of magnitude faster compared to the uncatalyzed reaction. The activity of MOF-808 was also demonstrated towards hen egg white lysozyme protein (HEWL), which was selectively fragmented under physiological pH. More recently, we also demonstrated the high potential of Zr-based POMs and MOFs in catalyzing the challenging peptide bond formation reaction directly from non-activated carboxylic acids and free amines. The amide bond formation reaction can be performed under mild conditions, low catalyst loading, and without the use of water scavengers, dry solvents or additives for facilitating the amine attack, in sharp contrast with most of other catalytic systems reported so far.

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