“Technology Development for Inhibitor Discovery of Chromatin Associated Proteins Linked to Lysine Methylation”
Seminar based upon the doctoral dissertation of Justin M. Rectenwald under the direction of Dr. Ken Pearce and Dr. Stephen Frye.
The identification of molecules that tightly bind to therapeutically relevant targets remains one of the biggest challenges in biomedical research. Continued development of discovery technologies that are cost effective, fast, reliable, and reproducible are essential for the generation of new tool compounds and potential therapeutics. A target-class driven strategy for discovery of potent and selective inhibitors is an approach adopted by many academic and industrial labs. Development of multiple, complementary strategies for hit discovery and characterization suitable for target-class approaches can greatly enhance the speed and dependability of biomedical research. Herein, is the description of a series
of technologies developed and applied to chromatin associated proteins involved in either the recognition or placement of methyl groups upon lysine residues of histone tails. A generalized TR-FRET assay and panel, a label-free mass-spectrometry catalytic assay, and a focused DNA-Encoded Library platform and their applications are summarized.