Development of fluorescence polarization assay for histone deacetylases

WCC 11

Shuo Xing,, Melanie Burger,, and James L. Gleason, Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, QC H3A 2K6, Canada
Hyperactivity of histone deacetylases (HDACs, important transcription regulators in eukaryotic systems) is closely linked to various forms of cancer. Consequently, many HDAC inhibitors (HDIs) have been proved efficient in cancer treatment. Current HDAC activity assays employed to assess HDI affinity and potency rely on either radioisotope labeling or colorimetric measurements of fluorogenic substrates. Due to the presence of multiple isoforms of HDACs in mammalian systems, commercially fluorogenic substrates fail to provide equal efficiency for many of the isoforms of interest. We are currently developing a novel assay based on fluorescence polarization using a fluorescein-coupled suberoylanilide hydroxamic acid (SAHA) derivative. SAHA is an approved anticancer agent, shown to bind to a variety of HDACs as an inhibitor. Potential HDI binding will be measured by displacement of the SAHA derivative and by the resulting change in fluorescence polarization. This method avoids the labour-intensive radiolabelling and affords a larger spectrum of HDACs.

The Merck Index Women in Chemistry
2:30 PM-4:30 PM, Monday, August 17, 2009 Walter E. Washington Convention Center -- Hall D, Poster

Women Chemists Committee

The 238th ACS National Meeting, Washington, DC, August 16-20, 2009