Zhang Yimeng, Liu Yan, Wu Xiaoqing, Lu Xingxing, Wang Meizi, Ye Dexing, Iqbal Chandni, Sun Wenyu, Zhang Xinyuan, Zhang Li, Yang Xinling
Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China.
Key Laboratory of National Forestry and Grassland Administration on Pest Chemical Control, China Agricultural University, Beijing 100193, China.
J Agric Food Chem. 2024 May 22;72(20):11341-11350. doi: 10.1021/acs.jafc.3c09231. Epub 2024 May 7.
Insect neuropeptides play an essential role in regulating growth, development, reproduction, nerve conduction, metabolism, and behavior in insects; therefore, G protein-coupled receptors of neuropeptides are considered important targets for designing green insecticides. Cockroach-type allatostatins (ASTs) (FGLamides allatostatins) are important insect neuropeptides in that inhibit juvenile hormone (JH) synthesis in the corpora allata and affect growth, development, and reproduction of insects. Therefore, the pursuit of novel insecticides targeting the allatostatin receptor (AstR) holds significant importance. Previously, we identified an AST analogue, , as a promising candidate for pest control. Herein, we first modeled the 3D structure of AstR in (AstR) and predicted the binding mode of with -AstR to study the critical interactions and residues favorable to its bioactivity. Based on this binding mode, we designed and synthesized a series of derivatives and assessed their insecticidal activity against . Among them, compound showed higher insecticidal activity than against by inhibiting JH biosynthesis, indicating that is a potential candidate for a novel insect growth regulator (IGR)-based insecticide. Moreover, exhibited insecticidal activity against , indicating that these AST analogs may have a wider insecticidal spectrum. The underlying mechanisms and molecular conformations mediating the interactions of with -AstR were explored to understand its effects on the bioactivity. The present work clarifies how a target-based strategy facilitates the discovery of new peptide mimics with better bioactivity, enabling improved IGR-based insecticide potency in sustainable agriculture.
昆虫神经肽在调节昆虫的生长、发育、繁殖、神经传导、新陈代谢和行为方面发挥着至关重要的作用；因此，神经肽的G蛋白偶联受体被认为是设计绿色杀虫剂的重要靶点。蟑螂型咽侧体抑制素（ASTs）（FGLamides咽侧体抑制素）是重要的昆虫神经肽，因为它们能抑制咽侧体中保幼激素（JH）的合成，并影响昆虫的生长、发育和繁殖。因此，研发针对咽侧体抑制素受体（AstR）的新型杀虫剂具有重要意义。此前，我们鉴定出一种AST类似物作为害虫防治的有潜力候选物。在此，我们首先对蜚蠊AstR（AstR）的三维结构进行建模，并预测该类似物与蜚蠊AstR的结合模式，以研究对其生物活性有利的关键相互作用和残基。基于这种结合模式，我们设计并合成了一系列该类似物的衍生物，并评估了它们对蜚蠊的杀虫活性。其中，化合物对蜚蠊的杀虫活性高于该类似物，通过抑制JH生物合成实现，表明该类似物是基于新型昆虫生长调节剂（IGR）的杀虫剂的潜在候选物。此外，该类似物对其他昆虫也表现出杀虫活性，表明这些AST类似物可能具有更广泛的杀虫谱。我们探索了介导该类似物与蜚蠊AstR相互作用的潜在机制和分子构象，以了解其对生物活性的影响。目前的工作阐明了基于靶点的策略如何促进发现具有更好生物活性的新型肽模拟物，从而在可持续农业中提高基于IGR的杀虫剂效力。
