2. Academic Validation
  3. A Novel Peptidomimetic Insecticide: Dippu-AstR-Based Rational Design and Biological Activity of Allatostatin Analogs

A Novel Peptidomimetic Insecticide: Dippu-AstR-Based Rational Design and Biological Activity of Allatostatin Analogs

  • J Agric Food Chem. 2024 May 22;72(20):11341-11350. doi: 10.1021/acs.jafc.3c09231.
Yimeng Zhang 1,  Yan Liu 1,  Xiaoqing Wu 1,  Xingxing Lu 1,  Meizi Wang 1,  Dexing Ye 1,  Chandni Iqbal 1,  Wenyu Sun 1,  Xinyuan Zhang 1,  Li Zhang 1 2,  Xinling Yang 1 2
Affiliations

Affiliations

  • 1 Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China.
  • 2 Key Laboratory of National Forestry and Grassland Administration on Pest Chemical Control, China Agricultural University, Beijing 100193, China.
PMID: 38713071 DOI: 10.1021/acs.jafc.3c09231
Abstract

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 Diploptera punctata 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, H17, as a promising candidate for pest control. Herein, we first modeled the 3D structure of AstR in D. punctata (Dippu-AstR) and predicted the binding mode of H17 with Dippu-AstR to study the critical interactions and residues favorable to its bioactivity. Based on this binding mode, we designed and synthesized a series of H17 derivatives and assessed their insecticidal activity against D. punctata. Among them, compound Q6 showed higher insecticidal activity than H17 against D. punctata by inhibiting JH biosynthesis, indicating that Q6 is a potential candidate for a novel insect growth regulator (IGR)-based insecticide. Moreover, Q6 exhibited insecticidal activity against Plutella xylostella, indicating that these AST analogs may have a wider insecticidal spectrum. The underlying mechanisms and molecular conformations mediating the interactions of Q6 with Dippu-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.

Keywords

Dippu-AstR-based rational design; allatostatin receptor; insecticidal activity; juvenile hormone; peptidomimetic.

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