Interactions of p-Nitrobenzene Diazonium Fluoroborate and Analogs with the Active Sites of Acetylcholine-Receptor and -Esterase

p-Nitrobenzene diazonium fluoroborate (NDF) is a potent inhibitor of the carbamylcholine-induced depolarization of the electroplax and of acetylcholinesterase. It probably forms covalent bonds with the acetylcholine-receptor and -esterase at the active site of the proteins. Its inhibitory strength i...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1970-09, Vol.67 (1), p.74-78
Main Authors: Mautner, Henry G., Bartels, Eva
Format: Article
Language:English
Subjects:
Acetylcholinesterase
Active sites
Alcohols - pharmacology
Animals
Binding Sites
Biochemistry
Biological Sciences: Biochemistry
Boron Compounds - pharmacology
Carbachol - pharmacology
Cholinesterase Inhibitors
Covalent bonds
Depolarization
Diazonium Compounds - pharmacology
Eels
Electric Organ - drug effects
Fluorine
Half lives
Hexamethonium Compounds - pharmacology
In Vitro Techniques
Nitrobenzenes - pharmacology
Quaternary Ammonium Compounds - pharmacology
Reagents
Receptors
Sulfur - pharmacology
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Summary:p-Nitrobenzene diazonium fluoroborate (NDF) is a potent inhibitor of the carbamylcholine-induced depolarization of the electroplax and of acetylcholinesterase. It probably forms covalent bonds with the acetylcholine-receptor and -esterase at the active site of the proteins. Its inhibitory strength is at least the same as that of trimethylammonium diazonium fluoroborate (TDF). The p-acetoxy analog, with its weaker electron-withdrawing group, is about ten times weaker as an inhibitor than the trimethylammonium or p-nitro analogs, both of which have strong electron-withdrawing groups. After treatment of the electroplax preparation with dithiothreitol, NDF remains an irreversible receptor-inhibitor, while TDF becomes a potent reversible receptor-activator. TDF is self-inhibitory: applied before reduction, it no longer depolarizes. Although the first observations on TDF suggested that the compound labels both proteins by virtue of the steric complementary of its trimethylammonium group to a negative subsite in the proteins, the present study indicates that it is the positively charged diazonium group that reacts with the active sites of the proteins to form a covalent bond with an appropriate amino-acid residue.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.67.1.74