CARB 100 |
| The nucleic acid-binding properties of aminoglycoside antibiotics were first described by Davies and coworkers in 1964, when it was found that streptomycin interfered with peptide synthesis (Davies et al., 1964). More than twenty years later, Moazed and Noller discovered that many aminoglycosides specifically interacted with prokaryotic 16S rRNA, interfering with tRNA binding and/or decoding of mRNA (Moazed & Noller, 1987). Neomycin was one such aminoglycoside identified in tRNA A-site binding, and since has been found to interact specifically with a wide array of nucleic acids that display diverse structure and function, including viral RNAs such as HIV-1 TAR. Because of this, neomycin has been used effectively as a scaffold in the development of high-affinity nucleic acid-targeting therapeutics (Arya, 2005). We have investigated the structural interaction between neomycin, Hoechst 33258 and HIV-1 TAR RNA. Using isothermal titration calorimetry and circular dichroism, we have measured ligand binding affinities, and through structural characterization of this complex by NMR spectroscopy, we aim to determine the mode of binding of these ligands, allowing for future development of more effective antiviral therapeutics. Davies, J., Gilbert, W., and Gorini, L. (1964) Proc. Natl. Acad. Sci. USA, 51, 883-890. Moazed, D. and Noller, H. F. (1987) Nature, 327, 389-394. Arya, D. P. (2005) Top. Curr. Chem,. 253, 149-178. |
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Nucleic Acid Therapeutics
9:00 AM-11:45 AM, Wednesday, March 28, 2007 McCormick Place North -- Room N226, Level 2, Oral
Division of Carbohydrate Chemistry |