Bacterial infections that are resistant to existing treatments are a significant global health concern. The T-box riboswitch is a novel potential target for antibacterial drug discovery. This noncoding RNA regulates gene expression primarily in Gram-positive bacteria. This regulation occurs as a result of specific interactions between the 5’ untranslated region of the mRNA and a non-aminoacylated tRNA molecule. Previous studies in our lab identified small molecules that likely bind a highly conserved element within this riboswitch, called the antiterminator, and modulate T-box riboswitch function. We investigated a series of analogs of these initial hit compounds in order to determine factors that help to confer specific recognition of the target RNA. Using a fluorescence-based binding assay with antiterminator model RNA variants, a subset of RNA-specific binding analogs was identified that also inhibited tRNA binding and T-box riboswitch function. Structure-activity relationships for binding specificity along with experimental and computational analysis of possible binding modes indicate the observed activity likely results from differing RNA binding modes.

Characterization of ligand-RNA binding specificity for T-box riboswitch antiterminator RNA

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.