Synthesis of fluorescent probes directed to the active site gorge of acetylcholinesterase.

Six organophosphorus compounds linked to fluorophore groups were prepared in an effort to selectively modify the active site of acetylcholinesterase and deliver probes to the gorge region. Two compounds that vary by the length of a methylene (CH2) group, pyrene-SO2NH(CH2)nNHC(O)CH2CH2P(O)(OEt)(F) (where n = 2 or 3) were found to be potent, irreversible inhibitors of recombinant mouse AChE (Ki approximately 10(5) M(-1) min(-1)). Size exclusion chromatography afforded a fluorescently-labeled cholinesterase conjugate.