Novel auxin probes on auxin receptors and signal transduction

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The regulation of gene expression by the hormone auxin is a crucial mechanism in plant development. Arabidopsis F-box protein TIR1 is a receptor for auxin and recent structural work has revealed the molecular mechanism of auxin perception. TIR1 is the substrate receptor of the ubiquitin-ligase complex SCF^<TIR1>. However, the detailed relations between signaling and physiological response are still unclear. We have developed two types of auxin probes to study auxin responses by chemical biological approach.1 : Novel synthetic auxin agonists and antagonists. These probes are specific to TIR1-mediated events in Arabidopsis and their mode of action in binding to TIR1 is confirmed by X-ray crystallographic analysis. Further we demonstrate the utility of these probes for the analysis of TIR1-mediated auxin signaling in the moss P. patens. Our work not only provides a new useful tool for plant chemical biology but also demonstrates the first example of a specific small molecule inhibitor of F-box protein-substrate recruitment.2: Novel auxin probes derived from natural products. Terfestatin A (TrfA), a novel auxin signaling inhibitor, was identified in a screen of Streptomyces sp. F40 extracts for inhibition of the expression of an auxin-inducible gene. However, the mode of action of TrfA has not been elucidated. To identify the active core structure, twenty-five derivatives of TrfA were synthesized and their inhibitory activities against auxin-inducible gene expression were evaluated. The structure-activity relationships revealed the essential active core structure of TrfA, 3-butoxy-4-methylbiphenyl-2, 6-diol, which will lead to the design of biotin-tagged active TrfA.