title: Homo- and hetero-dimers of inactive organophosphorous group binding at dual sites of AChE.
abstract: Homo- and hetero-dimers of inactive organophosphorous group(s) dramatically enhanced the acetylcholinesterase (AChE; EC 3.1.1.7) inhibiting potency, with the highest potency observed at a tether length of 6 methylene groups (6d) for the homodimers, and 7 methylene groups (8e) for the heterodimers. The docking model of Drosophila melanogaster AChE suggested that 6d and 8e bound at the catalytic and peripheral sites of AChE, in which two organophosphorous groups of 6d individually oriented towards TRP83 of catalytic sites and TRP321 of peripheral sites, and phthalicimide group of 8e was appropriately arranged for a π-π interaction with the phenyl ring of TYR330, furthermore, the organophosphorous group introduced hydrophobic interaction with TRP83. The compounds prepared in this work demonstrated high insecticidal activity to Lipaphis erysimi and Tetranychus cinnbarinus at the concentration 300mg/L.
authors.affiliation: State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
authors.forename: Qianfei
authors.initials: Q
authors.lastname: Zhao
authors.forename: Ruliang
authors.initials: R
authors.lastname: Xie
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Fang
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Mei
authors.forename: Jun
authors.initials: J
authors.lastname: Ning
authors.forename: Yun
authors.initials: Y
authors.lastname: Tang
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D019281:Dimerization; D004331:Drosophila melanogaster; D007306:Insecticides / Q000378:metabolism; D008958:Models, Molecular; D009943:Organophosphorus Compounds / Q000378:metabolism*
chemical_list: D007306:Insecticides; D009943:Organophosphorus Compounds; D000110:Acetylcholinesterase