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Thiol Modification By Pharmacologically Active Agents of the Diazeniumdiolate Class

Volume 3, Numéro 2, 2012, pp. 91-95
DOI: 10.1615/ForumImmunDisTher.2012006334
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RÉSUMÉ

Promising drug candidates of the diazeniumdiolate (NONOate) chemical family include several types of thiol modification among their mechanisms of action: 1) drugs designed to release nitric oxide (NO) on reaction with the thiol group of glutathione (GSH) arylate the GSH, a step that removes reducing equivalents from the cell; (2) a similar reaction of the drug with the thiol group of a protein changes its structure, leading to potentially impaired function and cell death; (3) the NO generated as a byproduct in the above reactions can undergo oxidation, leading to S-nitrosylation and S-glutathionylation; and (4) diazeniumdiolates can also generate nitroxyl, which reacts with thiol groups to form disulfides or sulfinamides.

CITÉ PAR
  1. Kaczmarek Monika Z., Holland Ryan J., Lavanier Stephen A., Troxler Jami A., Fesenkova Valentyna I., Hanson Charlotte A., Cmarik Joan L., Saavedra Joseph E., Keefer Larry K., Ruscetti Sandra K., Mechanism of action for the cytotoxic effects of the nitric oxide prodrug JS-K in murine erythroleukemia cells, Leukemia Research, 38, 3, 2014. Crossref

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