2. Academic Validation
  3. Acetyl-CoA Carboxylase Proteolysis-Targeting Chimeras: Conceptual Design and Application as Insecticides

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

  • J Agric Food Chem. 2024 Aug 28;72(34):18809-18815. doi: 10.1021/acs.jafc.4c02793.
Qi Xu 1,  Hao Feng 1,  Zhong Li 1 2,  Xusheng Shao 1 2 3 4
Affiliations

Affiliations

  • 1 Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
  • 2 State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
  • 3 Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
  • 4 Engineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
PMID: 39145990 DOI: 10.1021/acs.jafc.4c02793
Abstract

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 μg 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.

Keywords

acetyl-CoA carboxylase; insecticides; pomalidomide; proteolysis-targeting chimeras; spirotetramat enol.

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