title: Thiol Modification By Pharmacologically Active Agents of the Diazeniumdiolate Class.
abstract: 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.
authors.affiliation: Basic Science Program, SAIC-Frederick, Inc., Frederick, Maryland.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Maciag
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Holland
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Saavedra
authors.forename: Harinath
authors.initials: H
authors.lastname: Chakrapani
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Shami
authors.forename: Larry K
authors.initials: LK
authors.lastname: Keefer
keywords: diazeniumdiolate; nitric oxide; thiol