Prof. Dr. Amanda E. Hargrove

Duke University, Durham, NC, USA

The Hargrove lab is an interdisciplinary team that works at the interface of chemistry and biology, using organic chemistry tools to study the structure and function of disease-relevant RNAs. As part of our efforts to improve small molecule targeting strategies and gain fundamental insights into small molecule:RNA recognition, we are analyzing patterns in both RNA-biased small molecule chemical space and RNA topological space privileged for differentiation. We identified physicochemical, structural, and spatial properties of biologically active RNA ligands that are distinct from those of protein-targeted ligands, and elaboration of four RNA binding scaffolds into a library enriched with these properties has led to improved recognition of medicinally relevant RNA targets, including viral and long noncoding RNA structures. We now have a library of ~1,000 RNA-targeted ligands, both synthetic and commercial, that we will contribute to COVID19-NMR for screening, and we will follow up with medicinal chemistry optimization of any leads.