Acetyl-CoA Carboxylase Proteolysis-Targeting Chimeras: Conceptual Design and Application as Insecticides

被引：2

作者：

Xu, Qi ^{[1
]}

Feng, Hao ^{[1
]}

Li, Zhong ^{[1
,2
]}

Shao, Xusheng ^{[3
,4
]}

机构：

[1] East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China

[2] East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

[3] East China Univ Sci & Technol, Sch Pharm, Shanghai Frontier Sci Res Base Optogenet Tech Cel, Shanghai Key Lab Chem Biol,State Key Lab Bioreact, Shanghai 200237, Peoples R China

[4] East China Univ Sci & Technol, Engn Res Ctr Pharmaceut Proc Chem, Sch Pharm, Minist Educ, Shanghai 200237, Peoples R China

来源：

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY | 2024年 / 72卷 / 34期

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

proteolysis-targeting chimeras; spirotetramat enol; pomalidomide; acetyl-CoA carboxylase; insecticides; PROTEIN-DEGRADATION; PROTACS;

D O I：

10.1021/acs.jafc.4c02793

中图分类号：

S [农业科学];

学科分类号：

09 ;

摘要：

Novel approaches for pest control are essential to ensure a sufficient food supply for the growing global population. The development of new insecticides must meet rigorous regulatory requirements for safety and address the resistance issues of existing insecticides. Proteolysis-targeting chimeras (PROTACs), originally developed for human diseases, show promise in agriculture. They offer innovative insecticides tailored to overcome resistance, opening avenues for agricultural applications. In this study, we developed small-molecule degraders by incorporating pomalidomide as an E3 ligand. These degraders were linked to a ligand (spirotetratmat enol) targeting the ACC protein through a flexible chain, aiming to achieve the efficient control of insects. Compounds 9a-9d were designed, synthesized, and evaluated for biological activities and mechanisms. Among them, 9b exhibited superior potency against Aphis craccivora (LC50 = 107.8 mu g mL(-1)) compared to others and effectively degraded ACC proteins through the ubiquitin-proteasome system. These findings highlight the potential of utilizing PROTAC-based approaches in the development of insecticides for efficient pest control.

引用

页码：18809 / 18815

页数：7

共 35 条

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