Insight into the reactivity and molecular interactions between lanthanide containing polyoxometalatesand proteins.

Selective hydrolysis of amide bonds in proteins is one of the most important procedures in analytical biochemistry, biotechnology and modern proteomics. However, the extreme kinetic inertness of the peptide bond, with a half-life estimated between 250 and 600 years under physiological conditions, makes this a challenging task. Our preliminary studies have also shown that in addition to the selective hydrolysis of hen egg white lysozyme by [Ce(alfa-PW11O39)2]10-,[3] several other Ce(IV), Zr(IV) and Hf(IV)-substituted POMs are able to efficiently hydrolyze proteins under mild conditions. These results serve as a proof of principle for our concept in which a regioselective metaloprotease was created by combining the enzyme-like molecular recognition ability of the POM scaffold with the hydrolytic activity of a strong Lewis acid metal cation imbedded into the POM structure. Although these results on the protease activity of POMs are very promising and establish the potential of POMs as a novel class of artificial metaloproteases, virtually no information is available on the molecular mechanism of this novel reaction. The goal of this study is to understand the factors governing recognition, reactivity and selectivity of metal-substituted POMs towards selected proteins, as an essential step towards establishing a structure-activity relationship of POMs as regioselective reagents for protein cleavage. Understanding the molecular basis of the interaction between POMs and proteins will greatly contribute to the further design and development of POMs as artificial proteases. Novel proteases with improved selectivity and reactivity are especially needed in modern proteomics, which is a large-scale study of protein structure and function. The study will also further advance the chemistry of POMs, as the catalysis by POMs emerged as one of the most successful areas of fundamental and applied catalysis in recent decades.