An Integrated System Using Peptide Arrays to Assess Kinase and Nuclear Receptor Activities in Clinical Samples for Biomarker Development
Conference Recording Feb 07, 2013
About the Speaker
Bertrand R Jordan (CNRS emeritus research director, ret.), an academic molecular biologist with particular achievements in the field of molecular immunology, is the founder and coordinator of the Marseille-Nice Genopole genomics consortium and counselor to the CoreBio-PACA technical platform organisation.
AbstractA system developed around peptide microarrays on a porous, transparent substrate allows flow-through incubation and real-time measurement of signals in a variety of settings, with sophisticated software for data acquisition and interpretation. We present two applications dealing with kinase activity profiling and with nuclear receptor-coregulator interactions. Kinases play an essential role in cancer biology, and many of the current drugs are kinase inhibitors. Peptide arrays constructed with phosphorylation substrates (up to 256) provide kinase activity profiles from small tissue samples, and allow inhibitor profiling. New compounds can be compared to established drugs, on- and off-target effects ascertained and kinase activity patterns studied as biomarkers in pre-clinical and clinical drug development. Nuclear receptors are major regulatory elements, undergoing a conformational change upon ligand interaction which alters their binding preference for coregulators. Many drugs act as agonists or antagonists to this interaction. Arrays of peptides representing up to 155 coregulator proteins can be used to study the effect of putative drugs on binding of more than 20 different nuclear receptors, providing information on potency and specificity of these molecules. The large resulting datasets are analysed by specially developed software that supports the biological interpretation, up to and including pathway analysis.