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dc.contributor.advisorMaly, Dustin Jen_US
dc.contributor.authorGower, Carrieen_US
dc.date.accessioned2015-02-24T17:32:26Z
dc.date.submitted2014en_US
dc.identifier.otherGower_washington_0250E_14007.pdfen_US
dc.identifier.urihttp://hdl.handle.net/1773/27438
dc.descriptionThesis (Ph.D.)--University of Washington, 2014en_US
dc.description.abstractProtein kinases are involved in the regulation of many intracellular processes. Misregulation of these enzymes has been implicated in a variety of diseases making protein kinases viable drug targets. Despite this interest in protein kinases, the cellular function of many members of this large enzyme family is not well understood. Chemical and genetic methods are currently in place for studying the function of protein kinases. However, these methods fall short in that chemical tools often have multiple off-targets within the highly conserved kinome, while genetic tools remove both catalytic and non- catalytic kinase function from the cell. Intracellular antibodies developed through phage and ribosomal display have been shown to bind potently and selectively to protein kinases of interest without affecting catalytic function. Seeking to develop selective and potent bivalent inhibitors of protein kinases for use in cellular studies, we have employed a chemical genetic method involving a self-labeling protein to tether a promiscuous kinase inhibitor with various intracellular antibodies. Kinome-wide selectivity profiling has enabled us to determine that these bivalent inhibitors are highly selective for their desired targets. Through this method, it is conceivable that potent and selective inhibitors of any protein kinase of interest might be developed for use in cells.en_US
dc.format.mimetypeapplication/pdfen_US
dc.language.isoen_USen_US
dc.rightsCopyright is held by the individual authors.en_US
dc.subject.otherChemistryen_US
dc.subject.otherchemistryen_US
dc.titleSelective Bivalent Reagents for the Study of Protein Kinasesen_US
dc.typeThesisen_US
dc.embargo.termsDelay release for 1 year -- then make Open Accessen_US
dc.embargo.lift2016-02-24T17:32:26Z


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