Rational design of inhibitors of VirA-VirG two-component signal transduction |
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| Authors: | Maresh Justin Zhang Jin Tzeng Yih-Ling Goodman Nora A Lynn David G |
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| Affiliation: | Department of Chemistry, Center for Fundamental and Applied Molecular Evolution, Emory University, Atlanta, GA 30322, USA. |
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| Abstract: | VirA-VirG two-component system regulates the vir (virulence) operon in response to specific host factors (xenognosins) in the plant pathogen Agrobacterium tumefaciens. Using whole cell assays, stable inhibitors inspired by the labile natural benzoxazinone inhibitor HDMBOA are developed. It is found that aromatic aldehydes represent a minimal structural unit for activity. In particular, 3-hydroxy-4,6-dimethoxy-3H-isobenzofuran-1-one (HDI) was found to have the highest activity, making it the most potent developed inhibitor of virulence gene expression in Agrobacterium. |
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