PMID: 3768408Oct 29, 1986Paper

Inactivation of acetylcholinesterase with a bretylium tosylate photoaffinity probe

Biochimica Et Biophysica Acta
B R Branchini, E J Lajiness

Abstract

Azidobretylium tosylate (ABT), the p-azido analogue of bretylium tosylate, has been synthesized to serve as a photoaffinity probe for bretylium binding sites. Bretylium tosylate has antiarrhythmic action and also interacts with amiloride-sensitive sodium ion transport sites. Acetylcholinesterase was used as a model protein, and both bretylium and ABT are reversible inhibitors of this enzyme. The kinetic inhibition constants (Ki) were determined to be 40 microM for bretylium tosylate and 6 microM for ABT. The azido compound is photochemically labile and apparently irreversibly inactivates the enzyme. The rate was retarded by the addition of bretylium tosylate or 4-oxo-N,N,N-trimethylpentanaminium iodide (OTI). Sephadex G-25 chromatography further demonstrated the irreversible nature of the photoinactivation. Since ABT binds at or near the acetylcholinesterase active site, it may be a useful probe for the characterization of the enzyme active site.

References

Jan 1, 1978·Advances in Cardiology·J Koch-Weser
Jan 1, 1977·Methods in Enzymology·H Bayley, J R Knowles
Sep 1, 1973·Proceedings of the National Academy of Sciences of the United States of America·A E RuohoS J Singer
Aug 1, 1972·Analytical Biochemistry·K B Augustinsson, B Axenfors
Dec 1, 1970·Proceedings of the National Academy of Sciences of the United States of America·H KieferS J Singer
Jul 10, 1965·Nature·P E Leveque
Apr 1, 1966·The American Journal of Cardiology·M Bacaner
Dec 22, 1982·Biochimica Et Biophysica Acta·A IlaniM B Bacaner
Sep 1, 1955·Biochimica Et Biophysica Acta·I B WILSON, B GINSBURG
Jul 1, 1961·Biochemical Pharmacology·G L ELLMANR M FEATHER-STONE

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Citations

Sep 22, 1993·Molecular and Cellular Biochemistry·L Y Zang, H P Misra

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