Lanthanide containing polyoxometalate complexes as regioselective reagents for protein cleavage.

The aim of this project is to develope regioselective and non-invasive synthetis proteases by using polyoxometalate (POM) skeletons as ligands for the hydrolytically active metal ions. POMs are a tuneable class of metal-oxo compounds that are known to exhibit selective binding under physiological conditions to a range of different proteins through electrostatic and hydrogen-bonding interactions. By incorporating metal ions into the POM skeletons, functionalised POMs that non-covalently and non-invasively interacti with the positively charged protein regions will be created. The approach is very versatile: a range of metal functionalised POMs differing in shape, polarity and surface charge distribution will be synthesized and the structure-activity relationship toward selected proteins will be established. The interdisciplinary approach of combining inorganic synthesis and protein chemistry will be complemented by using high-resolution multinuclear magnetic resonance spectroscopy to reveal the ibnding site of metal-functionalised POMs and to determine the stability of the POM/protein complexes.

Keywords:Polyoxometalates, Lanthanides, Protein hydrolysis, Peptides, Amide bond, NMR spectroscopy

Disciplines:Biochemistry and metabolism, Systems biology, Medical biochemistry and metabolism, Inorganic chemistry