Tools and Tactics for Targeting RNA with Small Molecules
Thu, May. 4, 2023, 4:30pm
Taylor Auditorium, Frick Chemistry Lab B02
Host: Ralph Kleiner
Roughly 85% of the three billion bases in the human genome is transcribed into RNA, yet just 3% of these sequences code for polypeptides. In addition, only about 15% of the human proteome is considered “druggable”. However, broad efforts have demonstrated clear roles for both noncoding RNAs and so-called “undruggable” proteins in diverse human diseases. Small molecules capable of interacting with and modulating the function of RNA would thus have considerable potential as both probes of basic RNA biology and potential therapeutics for diseases with no cure. In this seminar, I will discuss our group’s efforts to identify, characterize, and study druglike small molecules that target diverse RNA structures. I will describe the development of machine learning algorithms to large high throughput screening datasets to characterize RNA binding chemical space. Finally, I will describe our efforts to target human mRNA transcripts that encode undruggable oncogenes and highlight the potential for this approach to enable the development of novel small molecule therapeutics. A particular emphasis of this work is the use of atomic resolution structure to inform the mechanism of action of RNA-targeting small molecules.