Global kinase screening. Applications of frontal affinity chromatography coupled to mass spectrometry in drug discovery.

Jacek J Slon-Usakiewicz, Jin-Rui Dai, William Ng, J Estelle Foster, Eugen Deretey, Leticia Toledo-Sherman, Peter R Redden, Andrew Pasternak, Neil Reid

Lead Discovery and Optimization Division, Protana Inc., 251 Attwell Drive, Toronto, Ontario, M9W 7H4 Canada.

Analytical chemistry 2005 Mar 1

filter terms:

Utilizing frontal affinity chromatography with mass spectrometry detection (FAC-MS), we have identified novel applications in the discovery of small-molecule hits to protein targets that are difficult if not impossible to accomplish using traditional assays. We demonstrate for the first time an ability to distinguish between competitive ligands for the ATP and substrate sites of protein kinase C independently in the same experiment and show that ATP competitive ligands using a functionally inactive receptor tyrosine kinase can be identified. This ability of FAC-MS to simultaneously monitor binding at the ATP and substrate binding sites, as well as measure ligand binding to both active and inactive kinases, suggests that FAC-MS can be used as a "global kinase binding assay".

Citation

Jacek J Slon-Usakiewicz, Jin-Rui Dai, William Ng, J Estelle Foster, Eugen Deretey, Leticia Toledo-Sherman, Peter R Redden, Andrew Pasternak, Neil Reid. Global kinase screening. Applications of frontal affinity chromatography coupled to mass spectrometry in drug discovery. Analytical chemistry. 2005 Mar 1;77(5):1268-74