Chemical Studies in Bacterial Cell Biology

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DESCRIPTION (provided by applicant): This application described experiments that will shed light on the bacterial cell cycle and elucidate ways in which this process might be targeted by small molecules to cure infections resistant to current antibiotics. Central to bacterial cell cycle is a protein called FtsZ, which is similar in structure to mammalian tubulin. Although many natural products and other small molecules target tubulin effectively, resulting in therapies for curing cancer, the ability to target the bacterial cell cycle and halt resistant infections has not been fully explored. We will develop efficient syntheses of several FtsZ-targeting natural products and we will use NMR spectroscopy to discern how these molecules interact with FtsZ. With this insight, we will then use computational chemistry to interpret the molecular interactions that result in binding and how to design more potent molecules. We will also use information provided by X-ray crystallography in the design of protein-mimicking small molecules that can disrupt bacterial cell division and possibly halt the bacterial response to DNA damage, which could render the organism more susceptible to current antibiotics.