2. Academic Validation
  3. Exploring unsymmetrical dyads as efficient inhibitors against the insect β-N-acetyl-D-hexosaminidase OfHex2

Exploring unsymmetrical dyads as efficient inhibitors against the insect β-N-acetyl-D-hexosaminidase OfHex2

  • Biochimie. 2014 Feb;97:152-62. doi: 10.1016/j.biochi.2013.10.008.
Qi Chen 1,  Peng Guo 2,  Lin Xu 2,  Tian Liu 1,  Xuhong Qian 3,  Qing Yang 4
Affiliations

Affiliations

  • 1 School of Life Science and Biotechnology, Dalian University of Technology, No.2 Linggong Road, Dalian, Liaoning 116024, China.
  • 2 State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
  • 3 State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China. Electronic address: xhqian@ecust.edu.cn.
  • 4 School of Life Science and Biotechnology, Dalian University of Technology, No.2 Linggong Road, Dalian, Liaoning 116024, China. Electronic address: qingyang@dlut.edu.cn.
PMID: 24140956 DOI: 10.1016/j.biochi.2013.10.008
Abstract

The GH20 β-N-acetyl-d-hexosaminidase OfHex2 from the insect Ostrinia furnacalis (Guenée) is a target potential for eco-friendly pesticide development. Although carbohydrate-based inhibitors against β-N-acetyl-D-hexosaminidases are widely studied, highly efficient, non-carbohydrate inhibitors are more attractive due to low cost and readily synthetic manner. Based on molecular modeling analysis of the catalytic domain of OfHex2, a series of novel naphthalimide-scaffold conjugated with a small aromatic moiety by an alkylamine spacer linker were designed and evaluated as efficiently competitive inhibitors against OfHex2. The most potent one containing naphthalimide and phenyl groups spanning by an N-alkylamine linker has a Ki value of 0.37 μM, which is 6 fold lower than that of M-31850, the most potent non-carbohydrate inhibitor ever reported. The straightforward synthetic manners as well as the presumed binding model in this paper could be advantageous for further structural optimization for developing inhibitors against GH20 β-N-acetyl-D-hexosaminidases.

Keywords

Enzyme inhibitors; Molecular docking; Naphthalimide; Tryptophan fluorescence titration; β-N-Acetyl-d-hexosaminidase.

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