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Could metals help treat cancer?

28.07.2008
A fruitful collaboration between chemists and biologists has made it
possible to identify the effects of a new class of molecules,
polyoxometalates(1), primarily composed of metals and oxygen.
These molecules are very powerful inhibitors of a specific protein kinase,
CK2, an enzyme that is overactive in a number of cancers. The enzyme's
instrumental role in controlling cell proliferation and survival makes
it an important target in the search for new medications.
These results have just been published in the journal Chemistry and Biology by
chemists from the Institut de chimie moléculaire (CNRS / UPMC) and
biologists from the Institut de recherche en technologies et sciences
pour le vivant (iRTSV, CEA de Grenoble / CNRS / Inserm).
*Phosphorylation enzymes (2), which include the protein kinase CK2, play
a critical role in controlling cell proliferation. Deregulated protein
kinase activity is implicated in a number of cancers, which has led to a
recent surge in research on molecules that can inhibit the activity of
these enzymes. The currently known CK2 inhibitors are all organic
compounds that neutralize enzymatic activity by binding to its active
site (3).
The contribution of the study carried out by the researchers at the
Institut de chimie moléculaire and the Institut de recherche en
technologies et sciences pour le vivant was to reveal a new class of CK2
inhibitors. The new inhibitors are inorganic molecules, polyoxometalates
(POMs), primarily made up of metals (molybdenum and tungsten) and
oxygen. They are the most powerful CK2 inhibitors yet discovered,
working at very low (nanomolar) concentrations. In addition, the
researchers showed that the mode of action of POMs, although not yet
fully understood, is completely new. Unlike organic inhibitors, POMs do
not bind to the active site of the enzyme.
This work opens up several areas for further research: clarifying the
mechanism of action of these new molecules, finding the minimum
molecular entity that can inhibit enzyme activity, and finally, given
its importance in the health field, improving knowledge of how the
enzyme CK2 works. In the longer term, these results could pave the way
for new approaches to developing anti-cancer drugs.
(1) Polyoxometalates are anionic inorganic metal oxide structures that
have valuable catalytic properties.
(2) Phosphorylation enzymes called protein kinases can attach a
phosphate group to proteins that may be inactive enzymes. The addition
of the phosphate group can activate these "silent" enzymes. Protein
kinases thus play a central role in controlling the activity of numerous
enzymes in the cell.
(3)The active site of an enzyme is a particular region where the
substrates bind together and enzymatic reactions takes place.

Julien Guillaume | alfa
Further information:
http://www.cnrs-dir.fr

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