Towards Guiding Principles for Targeting RNA: Rational Approaches to Design and Synthesize RNA-Biased Small Molecule Libraries
Brittany Morgan, Ph.D. candidate
Amanda Hargrove, advisor
Monday, June 18, 2018 - 9:00am to 10:00am
Location: French Family Science Center 4233
Avery, Meg

RNA is increasingly recognized as a therapeutic target in many diseases, including viral and bacterial infections, neurodegenerative disease, and cancer. To date, most RNA-targeted, small molecule screens utilize commercially available libraries, leading to low hit rates for RNA and/or the identification of promiscuous ligands with limited efficacy in biological systems. Therefore, the goal of my dissertation work is to elucidate guiding principles for selectively targeting RNA and utilize these rules to rationally design and synthesize novel RNA-biased libraries. Toward this goal, i) an oxazolidinone synthesis was developed, which was RNA-targeted, diversity-oriented and stereocontrolled; ii) a chemoinformatic analysis of bioactive, RNA-targeted ligands was performed, revealing key guiding principles for targeting RNA; and iii) a biology-oriented synthesis strategy was established to focus libraries to bioactive RNA chemical space. It is expected that the design strategies and guiding principles identified in this work will establish an avenue to create and/or select additional RNA-focused libraries, facilitating the discovery of novel RNA-targeted chemical probes and therapeutics.