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Enzyme fingerprints to advance drug discovery
09 October 2006
A technique to identify enzymes involved in the spread of cancer, could aid the development of new drugs.
Matrix metalloproteases (MMPs) are a family of enzymes involved in tissue remodelling, but maligant cancer cells can exploit these enzymes to promote the spread of tumors. The precise biological functions of many human MMPs remain largely unknown, so the development of methods to identify and characterise MMPs has become increasingly urgent.
Shao Qin Yao and colleagues at the National University of Singapore used click-chemistry methods, high yielding reactions that need only mild conditions, to make a series of small molecules that bind to MMPs. Each molecule, known as a probe, interacts with different enzymes to a different extent. The different levels of interaction were used to build up a unique profile, or fingerprint, of the enzyme.

Seven enzymes were fingerprinted with twelve probes - the strongest binding is visualized in red, and the weakest in green |
'Our work represents one of the few examples whereby enzymes immobilised on a microarray could be identified and characterised on the basis of their enzymatic properties,' said Yao.
The probes made by Yao's team are based on known inhibitors of metalloproteases, so as well as identifying new MMPs, the technique could be used to develop drugs that inhibit the action of MMPs involved in diseases like cancer, said Yao.
The researchers plan to extend their approach to other kinds of enzymes such as methyltransferases, which are used in DNA replication.
Laura Howes
References
J Wang, M Uttamchandani, J Li, M Hu and SQ Yao, Chem. Commun., 2006, 3783
DOI: 10.1039/b609446e
