title: A photoreactive probe that differentiates the binding sites of noncompetitive GABA receptor antagonists.
abstract: γ-Aminobutyric acid (GABA) receptors are postsynaptic membrane protein complexes that are important not only in the regulation of the nervous system but also as targets of drugs and insecticides. We synthesized a photoreactive straight-chain noncompetitive antagonist (NCA), 2-nitro-4-[3-(trifluoromethyl)-3H-diazirin-3-yl]phenyl 4-(4-methoxycarbonyl-1-butynyl)benzoate (NMB), to probe the NCA binding site. Our data show that this probe labels the NCA site and demonstrate that the NCA insecticide fipronil binds at a site distinct from that of other NCAs, such as picrotoxinin and 4'-ethynyl-4-n-propylbicycloorthobenzoate. The unique molecule NMB will be useful in identifying the cross-linking site of straight-chain NCAs in GABA receptors and mapping allosteric binding sites. Such studies should provide invaluable information in designing novel NCAs.
authors.affiliation: Department of Life Science and Biotechnology, Shimane University, Matsue, Shimane, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimotahira
authors.forename: Sayaka
authors.initials: S
authors.lastname: Fusazaki
authors.forename: Izumi
authors.initials: I
authors.lastname: Ikeda
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Ozoe
mesh_terms: D001665:Binding Sites; D018756:GABA Antagonists / Q000737:chemistry* / Q000378:metabolism; D015335:Molecular Probes; D010777:Photochemistry
chemical_list: D018756:GABA Antagonists; D015335:Molecular Probes