Vanadate in biological systems and its role as a phosphate analogue. Enzyme-selective inhibition of protein tyrosine phosphatases.

Vanadate is an insulin-mimetic compound that also has antitumor properties. It activates the function of a number of enzymes and inhibits that of others. One goal of current research is to understand as completely as possible the aqueous chemistry of vanadate and its role in metabolic processes. Extensive studies of vanadate interactions with metabolites have been undertaken as have inhibition studies of phosphate-transferring enzymes.

Protein tyrosine phosphatases catalyze dephosphorylation of tyrosine residues on proteins and play an essential role in the regulation of a variety of cellular responses. Work with these phosphatases is localised in two areas: i) the selective inhibition of CD45 and PTP1B by vanadate and its complexes and ii) inhibition by peptide-based phosphate analogues. For this latter work, nuclear magnetic resonance studies are being used to extract the conformation of enzyme-bound peptides. Molecular modelling is then used in simulated docking experiments to study specific interactions between the inhibitor and the protein. This information is utilized for the development of better and more highly selective vanadium-based inhibitors.