A photoreactive probe that differentiates the binding sites of noncompetitive GABA receptor antagonists
| Autor: | Izumi Ikeda, Sayaka Fusazaki, Hiroshi Shimotahira, Yoshihisa Ozoe |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Binding Sites
GABAA receptor Stereochemistry Chemistry Photochemistry Organic Chemistry Clinical Biochemistry Allosteric regulation Pharmaceutical Science respiratory system GABA receptor antagonist Biochemistry GABA Antagonists A-site chemistry.chemical_compound Molecular Probes Drug Discovery Molecular Medicine Binding site Receptor Molecular probe Molecular Biology Fipronil |
| Zdroj: | Bioorganicmedicinal chemistry letters. 21(6) |
| ISSN: | 1464-3405 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect