靶向独脚金内酯受体的新型植物生长调节剂的先导优化及作用机制研究

开发能调控植物生长发育和环境适应性的小分子对提高作物产量具有重要意义。本项目针对调节植物株型及提高抗旱性的关键科学问题，以独脚金内酯(SL)受体为作用靶标酶，设计兼具调节分枝和抗旱性的新型SL受体激动剂。基于申请人导师发现的SL受体的水解感知机制，在天然SL的药效团丁烯酸内酯结构中引入抗旱性亚结构单元，目标化合物被SL受体感知后激活SL信号通路调节植物分枝，同时被SL受体水解出抗旱性基团增强植物抗旱性，提高目标分子的靶向性及有效利用率。申请人前期利用此策略筛选出了能有效促进SL受体蛋白AtD14与下游蛋白AtMAX2互作的化合物ADSL。本项目将在此基础上，对其进行结构优化，结合其调节分枝及抗旱活性，建立定量构效关系模型，并研究候选化合物的作用机制。本项目的成功完成将为高活性SL受体激动剂的合理设计奠定理论基础，对开发兼具调节株型和抗旱性的新型植物生长调节剂具有重要的理论及应用价值。

The development of small molecules that can regulate plant growth and development and environmental adaptability is of great significance for improving crop yield. This project is aimed at the key scientific issues of regulating plant type and enhancing its drought resistance, and proposes to design novel strigolactone (SL) receptor agonists with SL receptor as the target. Based on the hydrolysis perception mechanism of SL receptor discovered by the applicant's supervisor, substructures with drought-resistant activity was introduced into the pharmacophore butenolide of natural SL. Target compounds will trigger SL signaling pathway regulating plant branching by SL receptor, and SL receptor will hydrolyze target compounds into the drought-resistant substructure that could enhance plant drought resistance, which improving the targeting and medicinal efficiency of target compounds. In the previous study, the applicant used this strategy to screen out the compound ADSL that effectively promotes the interaction between the SL receptor protein AtD14 and the downstream protein AtMAX2. Based on previous study, this project will optimize the structure of compound ADSL, and establish a quantitative structure-activity relationship model based on their activities with regulating branches and drought resistance. The mechanism of action of candidate compounds was also studied. The successful completion of this project will provide theoretical foundation for the rational design of highly active SL receptor agonists, and will be of theoretical and applied significance for the development of novel plant growth regulator that can both efficiently regulate plant type and drought resistance.