title: Synthesis of a novel [125I]neonicotinoid photoaffinity probe for the Drosophila nicotinic acetylcholine receptor.
abstract: The insect nicotinic acetylcholine receptor (nAChR) is the target for the major insecticide imidacloprid (IMI) and for the first candidate photoaffinity probe described here. Addition to 1-[(6-chloro-3-pyridinyl) methyl]-4,5-dihydro-2-nitromethylene-1H-imidazolidine (the nitromethylene analog of the nitroimine IMI) of formaldehyde and any one of several primary amines is known to give hexahydro-8-nitroimidazo[1,2-c]pyrimidine derivatives. These imidazopyrimidines with a wide range of N-substituents were found to inhibit [3H]IMI binding to the Drosophila or Musca nAChR by 50% (IC50) at 0.7-38 nM. Esterification of the N-(2-hydroxyethyl) derivative with 2-azido-5-(trimethylstannyl)-benzoic acid and then iododestannylation using Na125I and chloramine-T provide the candidate photoaffinity probe 6-[2-(2-azido-5-[125I]iodobenzoyl) ethyl]-1-[(6-chloro-3-pyridinyl)methyl]-1,2,3,5,6,7-hexahydro-8 -nitroimidazo[1,2-c]pyrimidine. This compound (unlabeled) has an IC50 of 8 nM for [3H]-IMI binding in Drosophila head membranes, and the 125I-labeled photoaffinity probe labels only a 66 kDa protein(s) at a specific site inhibited by (-)-nicotine, consistent with the insecticide-binding subunit of the nAChR.
authors.affiliation: Department of Environmental Science, Policy, and Management, University of California, Berkeley 94720-3112, USA.
authors.forename: B
authors.initials: B
authors.lastname: Latli
authors.forename: M
authors.initials: M
authors.lastname: Tomizawa
authors.forename: J E
authors.initials: JE
authors.lastname: Casida
mesh_terms: D000345:Affinity Labels / Q000138:chemical synthesis*; D000818:Animals; D004330:Drosophila; D007093:Imidazoles / Q000378:metabolism; D007306:Insecticides / Q000378:metabolism; D009117:Muscidae; D000073943:Neonicotinoids; D009539:Nicotinic Acids / Q000138:chemical synthesis* / Q000378:metabolism; D009574:Nitro Compounds; D011950:Receptors, Cholinergic / Q000378:metabolism*
chemical_list: D000345:Affinity Labels; D007093:Imidazoles; D007306:Insecticides; D000073943:Neonicotinoids; D009539:Nicotinic Acids; D009574:Nitro Compounds; D011950:Receptors, Cholinergic; C082359:imidacloprid