Chromodomain-Peptide Displacement Assays for Inhibitor Discovery (2016)
Undergraduate: Amy Lee
Faculty Advisor: Kenneth Pearce
Department: Global Studies
Post-translational modifications on protein¿¿¿s histone-binding domains may lead to regulation of transcription and chromatin structure. Methyl lysine readers are proteins that recognize methyl-lysine in histones and other regulatory proteins. These interactions are highly specific depending on the site and methylation state of the specific lysine residues. A number of these domains have been implicated in numerous disease states; therefore, identifying the small-molecule chemical probes that relates to specific histone binding has significant therapeutic potential. A high-throughput screening assay for the discovery of inhibitors of methyl-lysine binding proteins will be used to initiate a full-scale discovery effort for this broad target class. Amplified Luminescence Proximity Homogenous Assay (AlphaScreen¿¿¿) technology is used to detect domain interactions with various small-molecule chemical probes, then modifications of the probe's chemical structure are made for the most optimal binding. The result has the potential to be utilized for cellular reprogramming, ultimately leading to drug discovery.