The role of targeted chemical proteomics in pharmacology

Institute of Cancer Therapeutics, University of Bradford, Tumbling Hill Street, Bradford, West Yorkshire, UK.
British Journal of Pharmacology (Impact Factor: 4.84). 11/2011; 166(2):457-75. DOI: 10.1111/j.1476-5381.2011.01778.x
Source: PubMed


Traditionally, proteomics is the high-throughput characterization of the global complement of proteins in a biological system using cutting-edge technologies (robotics and mass spectrometry) and bioinformatics tools (Internet-based search engines and databases). As the field of proteomics has matured, a diverse range of strategies have evolved to answer specific problems. Chemical proteomics is one such direction that provides the means to enrich and detect less abundant proteins (the 'hidden' proteome) from complex mixtures of wide dynamic range (the 'deep' proteome). In pharmacology, chemical proteomics has been utilized to determine the specificity of drugs and their analogues, for anticipated known targets, only to discover other proteins that bind and could account for side effects observed in preclinical and clinical trials. As a consequence, chemical proteomics provides a valuable accessory in refinement of second- and third-generation drug design for treatment of many diseases. However, determining definitive affinity capture of proteins by a drug immobilized on soft gel chromatography matrices has highlighted some of the challenges that remain to be addressed. Examples of the different strategies that have emerged using well-established drugs against pharmaceutically important enzymes, such as protein kinases, metalloproteases, PDEs, cytochrome P450s, etc., indicate the potential opportunity to employ chemical proteomics as an early-stage screening approach in the identification of new targets.

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Available from: Chris Sutton, Nov 17, 2014
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    • "In pharmacology, chemical proteomics have been utilized to determine the specificity of drugs and their analogs, for anticipated as well as unknown targets that may also bind to the probe.41 These activity-based probes can specifically target diverse sets of enzyme families and provides direct information about the activation state of identified proteins.82 Several kinds of chemical probes have been used in proteomic studies across a multitude of enzyme classes such as hydrolases, proteases, kinases, phosphatases, histone deacetylases, glycosidases, and oxidoreductases.83 "
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