MEDI 283 |
| This talk will outline our design of synthetic ligands to modulate cell-cell communication in bacteria. Gram-negative bacteria use a chemical language of small molecules and their cognate protein receptors to monitor their local population density in a phenomenon known as quorum sensing. Quorum sensing regulated behaviors play a central role in bacterial pathogenesis. The development of chemical methods to attenuate bacterial quorum sensing would represent a powerful new strategy to control infectious disease. We have designed and synthesized synthetic ligands capable of intercepting quorum sensing pathways using computational, synthetic organic, and combinatorial chemistry techniques. This research has delivered a robust solid-phase synthetic route to non-natural N-acyl homoserine lactones. We have applied this route to the synthesis of multiple focused libraries, and examination of these libraries in reporter gene assays has revealed a set of potent quorum sensing antagonists and agonists. This talk will present our on-going studies of these compounds, including their evaluation against a range of relevant Gram-negative strains and in functional assays, e.g., biofilm formation. |
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Medicinal Chemistry Award Symposium
9:00 AM-12:10 PM, Tuesday, 12 September 2006 Moscone Center -- Room 102, Oral
Division of Medicinal Chemistry |