Helen Murray Free Endowed Lectures

Wishart Hall, Lean Lecture

Modulating the conformation and function of disease-relevant RNA with small molecules

Technical Lecture

Amanda Hargrove, PhD

Duke University, Durham, N.C.

• Professor of Chemistry, Duke Univeristy
• Associate Professor of Biochemistry, Duke University Medical School
• Board of Advisors, Trinity University Chemistry Department (2023-Present)
• Scientific Advisory Board Member, Arrakis Therapeutics (2021-Present)
• Editor-in-Chief: Medicinal Research Reviews (2019-Present)
• Editorial Board Member: Current Protocols; Chemical Communications; Supramolecular Chemistry

The College of Wooster students are invited to a “Get to Know Me” lunch immediately following the technical lecture in Severance 105.

Small molecules offer a unique opportunity to target structural and regulatory elements in therapeutically relevant RNAs, but understanding functional selectivity has been a recurrent challenge in small molecule:RNA recognition.  RNAs tend to be more dynamic and offer less chemical functionality than proteins, and biologically active ligands must compete with the highly abundant and highly structured RNA of the ribosome. Indeed, the first and only small molecule drug targeting RNA other than the ribosome was approved by the US FDA in August of 2020. Our recent survey of the literature revealed less than two hundred reported chemical probes that target non-ribosomal RNA in biological systems.

As part of our efforts to improve small molecule targeting strategies and gain fundamental insights into small molecule:RNA recognition, we have analyzed patterns in both RNA-biased small molecule chemical space and RNA topological space privileged for differentiation. We have applied these principles to functionally modulate conformations of 3’-triple helix of the long noncoding RNA MALAT1, leading to small molecule degraders, as well as in the development of RNA-targeted antivirals for enterovirus (EV71) and SARS-CoV-2.