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The tetrazole analogue of the auxin indole-3-acetic acid binds preferentially to TIR1 and not AFB5
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Quareshy, Mussa, Prusińska, Justyna, Kieffer, Martin, Fukui, Kosuke, Pardal , Alonso Javier, Lehmann, Silke, Schäfer, Patrick, Del Genio, Charo I., Kepinski, Stefan, Hayashi, Kenichiro, Marsh, Andrew and Napier, R. (Richard) (2018) The tetrazole analogue of the auxin indole-3-acetic acid binds preferentially to TIR1 and not AFB5. ACS Chemical Biology, 13 (9). pp. 2585-2594. doi:10.1021/acschembio.8b00527 ISSN 1554-8929.
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WRAP-tetrazole-analogue-auxin-acetic-binds-Quareshy-2018.pdf - Accepted Version - Requires a PDF viewer. Download (3921Kb) | Preview |
Official URL: https://doi.org/10.1021/acschembio.8b00527
Abstract
Indole-3-acetic acid (auxin) is considered one of the cardinal hormones in plant growth and development. It regulates a wide range of processes throughout the plant. Synthetic auxins exploit the auxin-signaling pathway and are valuable as herbicidal agrochemicals. Currently, despite a diversity of chemical scaffolds all synthetic auxins have a carboxylic acid as the active core group. By applying bio-isosteric replacement we discovered that indole-3-tetrazole was active by surface plasmon resonance spectrometry, showing that the tetrazole could initiate assembly of the Transport Inhibitor Resistant 1 (TIR1) auxin coreceptor complex. We then tested the tetrazole’s efficacy in a range of whole plant physiological assays and in protoplast reporter assays, which all confirmed auxin activity, albeit rather weak. We then tested indole-3-tetrazole against the AFB5 homologue of TIR1, finding that binding was selective against TIR1, absent with AFB5. The kinetics of binding to TIR1 are contrasted to those for the herbicide picloram, which shows the opposite receptor preference, as it binds to AFB5 with far greater affinity than to TIR1. The basis of the preference of indole-3-tetrazole for TIR1 was revealed to be a single residue substitution using molecular docking, and assays using tir1 and afb5 mutant lines confirmed selectivity in vivo. Given the potential that a TIR1-selective auxin might have for unmasking receptor-specific actions, we followed a rational design, lead optimization campaign, and a set of chlorinated indole-3-tetrazoles was synthesized. Improved affinity for TIR1 and the preference for binding to TIR1 was maintained for 4- and 6-chloroindole-3-tetrazoles, coupled with improved efficacy in vivo. This work expands the range of auxin chemistry for the design of receptor-selective synthetic auxins.
| Item Type: | Journal Article | ||||||||||||
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| Subjects: | Q Science > QK Botany | ||||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) Faculty of Science, Engineering and Medicine > Science > Mathematics |
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| Library of Congress Subject Headings (LCSH): | Auxin, Growth (Plants) -- Physiological aspects, Carboxylic acids, Tetrazoles, Indole | ||||||||||||
| Journal or Publication Title: | ACS Chemical Biology | ||||||||||||
| Publisher: | American Chemical Society | ||||||||||||
| ISSN: | 1554-8929 | ||||||||||||
| Official Date: | 21 September 2018 | ||||||||||||
| Dates: |
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| Volume: | 13 | ||||||||||||
| Number: | 9 | ||||||||||||
| Page Range: | pp. 2585-2594 | ||||||||||||
| DOI: | 10.1021/acschembio.8b00527 | ||||||||||||
| Status: | Peer Reviewed | ||||||||||||
| Publication Status: | Published | ||||||||||||
| Reuse Statement (publisher, data, author rights): | “This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Chemical Biology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/page/policy/articlesonrequest/index.html” | ||||||||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||||||||
| Date of first compliant deposit: | 30 August 2018 | ||||||||||||
| Date of first compliant Open Access: | 23 August 2019 | ||||||||||||
| RIOXX Funder/Project Grant: |
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