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Chemistry & Biochemistry Colloquium – Dr. Christine Chow – Wayne State University – Aminoglycoside Binding to Ribosomal RNAs: New Compounds and New Targets
March 15 @ 3:00 pm - 4:15 pm
Aminoglycoside binding to ribosomal RNAs: new compounds and new targets
Naturally occurring aminoglycosides (AGs) display high potency against a broad range of bacterial species. Nonetheless, development of bacterial resistance and adverse side effects such as ototoxicity are major challenges in using these compounds as antibiotics. Some recently discovered modified AGs maintain their desired antibacterial properties, but display reduced side effects, including diminished mitochondrial ribosome binding and lower ototoxicity. The objective of this study was to determine the relative binding affinities of AG analogues against bacterial and mitochondrial rRNAs by using a fluorescence-based assay, and examine AG-induced structural changes of rRNA motifs such as helix 44 (h44) of 16S rRNA and helix 69 (H69) of 23S rRNA by using NMR spectroscopy. Chemical footprinting was employed to determine AG binding sites on complete bacterial ribosomes, as well as examine selectivity of natural AGs or the analogues towards the bacterial A site. These results will lead to a better understanding of drug-rRNA interactions at the molecular level.