The Tetrazole Analogue of the Auxin Indole-3-acetic Acid Binds Preferentially to TIR1 and Not AFB5.
The Tetrazole Analogue of the Auxin Indole-3-acetic Acid Binds Preferentially to TIR1 and Not AFB5.
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生长素吲哚-3-乙酸的四唑类似物优先与 TIR1 结合，而不与 AFB5 结合。
DOI：
10.1021/acschembio.8b00527
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发表时间：
2018
影响因子：
4
通讯作者：
Quareshy M
中科院分区：
文献类型：
--
作者：
Quareshy M
吲哚-3-乙酸（生长素）被认为是植物生长发育的主要激素之一。它调节整个工厂的各种过程。合成生长素利用生长素信号传导途径，并且作为除草农用化学品是有价值的。目前，尽管化学支架的多样性，所有合成生长素具有羧酸作为活性核心基团。通过应用生物电子等排置换，我们发现吲哚-3-四唑是活性的表面等离子体共振光谱，表明四唑可以启动组装的运输抑制剂抗性1（TIR 1）生长素辅助受体复合物。然后，我们测试了四唑的功效在一系列的全植物生理测定和原生质体报告基因测定，这都证实了生长素的活性，虽然相当弱。然后，我们测试了吲哚-3-四唑对TIR 1的AFB 5同源物的作用，发现结合对TIR 1具有选择性，而对AFB 5则没有。与TIR 1结合的动力学与除草剂氨氯吡啶酸的动力学相反，氨氯吡啶酸显示出相反的受体偏好，因为它与AFB 5结合的亲和力远大于TIR 1。利用分子对接技术揭示了吲哚-3-四唑对TIR 1的偏好性的基础是一个单一的残基取代，并且使用TIR 1和afb 5突变株的测定证实了体内选择性。鉴于潜在的TIR 1选择性生长素可能有揭露受体特异性的行动，我们遵循合理的设计，铅优化运动，和一组氯化吲哚-3-四唑合成。4-氯吲哚-3-四唑和6-氯吲哚-3-四唑对TIR 1的亲和力和结合TIR 1的优先性得到改善，同时体内效力也得到改善。这项工作扩大了生长素化学的范围，用于受体选择性合成生长素的设计。
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 usingtir1andafb5mutant lines confirmed selectivityin 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 efficacyin vivo. This work expands the range of auxin chemistry for the design of receptor-selective synthetic auxins.
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植物生长调节剂的研究：十七．
DOI：
--
发表时间：
1949
期刊：
影响因子：
--
作者：
H. Veldstra;H. Booij
通讯作者：
H. Booij
影响因子：
7.4
作者：
Ward Steenackers;I. Cesarino;Petr Klíma;M. Quareshy;Ruben Vanholme;Sander Corneillie;Robert P. Kumpf;Dorien Van de Wouwer;K. Ljung;G. Goeminne;O. Novák;E. Zažímalová;R. Napier;W. Boerjan;B. Vanholme
通讯作者：
Ward Steenackers;I. Cesarino;Petr Klíma;M. Quareshy;Ruben Vanholme;Sander Corneillie;Robert P. Kumpf;Dorien Van de Wouwer;K. Ljung;G. Goeminne;O. Novák;E. Zažímalová;R. Napier;W. Boerjan;B. Vanholme
影响因子：
7.4
作者：
Walsh, Terence A.;Neal, Roben;Davies, John P.
通讯作者：
Davies, John P.
影响因子：
3
作者：
Price, Gareth W.;Gould, Phillip S.;Marsh, Andrew
通讯作者：
Marsh, Andrew
氨基苯甲酸衍生物的四唑类似物1
DOI：
--
发表时间：
1959
期刊：
影响因子：
--
作者：
J. Mcmanus;R. M. Herbst
通讯作者：
R. M. Herbst