Yuan Pengtao, Jiang Xi, Ni Xintong, Shao Xusheng, Qian Xuhong, Yang Qing
Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Key Laboratory of Synthetic Biology, Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.
State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, China.
J Enzyme Inhib Med Chem. 2025 Dec;40(1):2528056. doi: 10.1080/14756366.2025.2528056. Epub 2025 Jul 7.
Chitinase h (Chi-h) has been identified as a promising pesticide target due to its exclusive distribution in lepidopteran insects and its essential role in the moulting processes. In this study, we leverage Chi-h from destructive agricultural pest (Asian corn borer) as a model target to identify novel chitinase inhibitors. A conformational restriction approach was employed to design a series of novel Chi-h inhibitors. Among these, compound showed the highest inhibitory activity against Chi-h, with a value of 58 nM. Molecular docking analysis suggested that tightly bound to three subsites (-3 to -1) of Chi-h. The binding mode is further confirmed by the co-crystallization data of with the ChiA, a bacterial homologue of Chi-h, at a resolution of 1.8 Å. This research presents a novel approach for the development of highly potent insect chitinase inhibitors, offering potential tools for effective pest control.
几丁质酶h（Chi-h）因其在鳞翅目昆虫中的独特分布及其在蜕皮过程中的关键作用，已被确定为一个有前景的农药作用靶点。在本研究中，我们以破坏性农业害虫（亚洲玉米螟）的Chi-h为模型靶点，以鉴定新型几丁质酶抑制剂。采用构象限制方法设计了一系列新型Chi-h抑制剂。其中，化合物对Chi-h表现出最高的抑制活性，IC50值为58 nM。分子对接分析表明，该化合物与Chi-h的三个亚位点（-3至-1）紧密结合。该化合物与Chi-h的细菌同源物ChiA在1.8 Å分辨率下的共结晶数据进一步证实了这种结合模式。本研究提出了一种开发高效昆虫几丁质酶抑制剂的新方法，为有效控制害虫提供了潜在工具。
