| 9026029 |
Latli B, Tomizawa M, Casida JE: Synthesis of a novel [125I] neonicotinoid photoaffinity probe for the Drosophila nicotinic acetylcholine receptor. Bioconjug Chem. 1997 Jan-Feb;8(1):7-14.
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. |
82(1,1,1,2) |