This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Protein and lipid kinases are important transducers of cellular information. There are 500+ protein kinases and 30+ lipid kinases in the human genome. We are interested in developing chemical approaches for understanding and deciphering kinase mediated signaling pathways. The goal of this project is to develop highly selective small molecule protein and lipid kinase inhibitors. These small molecules are designed to fit in the ATP binding pocket of the kinases. We use synthetic organic chemistry coupled with structural biology (X-ray co-crystal structures) to develop these molecules. We typically use focused syntheses of five or fewer steps and make on the order of 20 candidate inhibitors per design. This work requires standard structural characterization of the intermediates and final products for publication or structural assignment purposes. Typically we need high resolution mass spectrometry of the small molecules. They are often highly structurally related, allowing for parameters to be optimized and used for a number of samples at once.
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