Journal article

Rational Design of an Organometallic Glutathione Transferase Inhibitor

Wee Han Ang, Lorien J Parker, Anastasia De Luca, Lucienne Juillerat-Jeanneret, Craig J Morton, Mario Lo Bello, Michael W Parker, Paul J Dyson

Angewandte Chemie - International Edition | WILEY-V C H VERLAG GMBH | Published : 2009


Double trouble: A hybrid organic-inorganic (organometallic) inhibitor was designed to target glutathione transferases. The metal center is used to direct protein binding, while the organic moiety acts as the active-site inhibitor (see picture). The mechanism of inhibition was studied using a range of biophysical and biochemical methods.


Funding Acknowledgements

We thank Mike Gorman and Guido Hansen for advice and encouragement and Julian Adams for help at the Australian Synchrotron. This work was supported by the Australian Synchrotron Research Program, which is funded by the Commonwealth of Australia under the Major National Research Facilities Program. Use of the Advanced Photon Source was supported by the U.S. DOE, Basic Energy Sciences, Office of Energy Research. This work was also supported by grants from the Australian Research Council (ARC) and the Australian Cancer Research Foundation. L.J.P was supported by a National Health and Medical Research Council of Australia (NHMRC) Dora Lush Scholarship and an International Centre for Diffraction Data Crystallography Scholarship. M.W.P. is an ARC Federation Fellow and NHMRC Honorary Fellow. The Swiss National Science Foundation also provided financial support.