Insight into the selectivity of metal-substituted polyoxometalates as a novel class of artificial proteases: combined experimental and theoretical approach.

The identification of novel primary sequences in the protein universe is expanding at an increasing rate. However, eludication of the three dimensional protein structure and function is seriously running behind. Because of the high complexity and the large size of these biomolecules, most of the currently used approaches for unraveling their structure and function of require protein hydrolysis into more manageable peptide fragments. Proteolytic enzymes have been used for this purpose, but their tendency to cleave proteins at too many places often leads to formation of short fragments that are difficult to identify. A few existing synthetic reagents are able to cleave proteins under harsh conditions, but they do so with only partial selectivity and with low yields. Therefore, the search for new synthetic proteases that are capable of cleaving proteins in a selective manner and under mild conditions is an area of great interest. A conceptually new approach has been recently discovered, combining the enzyme-like molecular recognition ability of a polyoxometalate (POM) scaffold with the hydrolytic activity of a strong Lewis acid metal cation imbedded into the POM structure. The aim of this project is to obtain insight into the mechanistic pathways governing bio-activity (recognition, selectivity, reactivity) of such Zr-POMs at a molecular level, by combining experimental and theoretical approaches.