ORGN 501 |
| M.-E. Duban, Searle Chemistry Laboratory 434, 5735 S. Ellis Avenue, and Department of Biochemistry and Molecular Biology, Searle Chemistry Laboratory 434, 5735 S. Ellis Avenue, and Department of Biochemistry and Molecular Biology, 920 E. 58th Street, The University of Chicago, Chicago, IL 60637-5415* |
| A. tumefaciens, α-2 proteobacterium and near relative of human pathogens, takes advantage of host wounds to initiate cancerous phytopathologies, the only cellular infectious agent capable of such. Pathogenesis begins on its exposure to specific wound phenols. Data substantiate that the phenols mediate transition to the virulent phenotype as agonists, making this an accessible example of receptor-mediated eubacterial pathogenesis. Prompted by difficulties in receptor identification, we dissected this process via agonist and antagonist design and synthesis, and via 3D modeling, a first application of modern pharmacologic methods to bacterial sensing. New formal molecule and activity descriptors led to the first quantitative models of this process, through which we observe that the paradigmatic agonist acetosyringone is neither a representative nor a highly potent agonist, that common agonists likely act by more than one mechanism, that agonist basal activity and potency are defined by distinct, complex interplays of substituent effects, etc, results which bear on design of further potent effectors. This work was supported by NIH NRSA GM07183-18 and by internship from Computer-Aided Molecular Design, R47E, Pharmaceutical Products Division, Abbott Laboratories (YC Martin, Sr. Project Leader). |
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Total Synthesis, Asymmetric Reactions and Syntheses, Bioorganic
9:00 AM-11:00 AM, Wednesday, March 31, 2004 Anaheim Convention Center -- Hall C, Poster
Division of Organic Chemistry |