Poster number 48 submitted by Jose Reyes Franceschi
Development of a chemo-transcriptomic platform for identifying RNA-binding small molecules
Jose A. Reyes Franceschi (Program in Chemical Biology, University of Michigan ), Emilio L. Cardenas, PhD (Department of Medicinal Chemistry, University of Michigan ), Prof. Amanda L. Garner, PhD (Department of Medicinal Chemistry, University of Michigan )
Dysregulation of RNA functions has been implicated in multiple human pathologies, such as bacterial and viral infections, as well as playing a role in other diseases including cancers. Because of RNAs’ involvement in diseases, the transcriptome has become an area of interest in the field of drug discovery. Current efforts for targeting RNA with small molecules has yielded therapeutics that treat bacterial infections and cancer; however, these target a small number of RNA molecules meaning that this field is still vastly underexplored. One big reason for the lack of RNA-targeting therapeutics is the lack of technologies for accurately screening RNA-binding small molecules in cells. This is a major issue since RNA is a very dynamic biomolecule whose structure depends upon its surrounding environment. Therefore, it is important to develop new approaches that allow us to screen for RNA-binding small molecules in living cells. In this project, we explore the synthesis and biological characterization of novel chemical probes that can help elucidate small molecule-RNA interactions in cells. This probe will consist of a small molecule fragment of interest linked to an RNA-selective covalent warhead that will react with the RNA to enable its covalent modification, and subsequent identification via affinity purification and sequencing. Efforts toward the development of this approach will be discussed.
Keywords: RNA, Small Molecule, Chemical Probe