Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylcholinesterase / chemistry*
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Acetylcholinesterase / metabolism*
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Animals
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Binding Sites
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Chromatography, Gel
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Fluorescent Dyes / chemical synthesis*
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Fluorescent Dyes / pharmacokinetics*
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Kinetics
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Mice
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Molecular Conformation
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Molecular Structure
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Organophosphorus Compounds / chemical synthesis*
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Organophosphorus Compounds / pharmacokinetics
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Structure-Activity Relationship
Substances
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Fluorescent Dyes
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Organophosphorus Compounds
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Recombinant Proteins
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Acetylcholinesterase