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Forum on Immunopathological Diseases and Therapeutics
SJR: 0.309 SNIP: 0.041 CiteScore™: 0.18

ISSN Imprimir: 2151-8017
ISSN On-line: 2151-8025

Archives: Volume 1, 2010 to Volume 7, 2016

Forum on Immunopathological Diseases and Therapeutics

DOI: 10.1615/ForumImmunDisTher.2012006334
pages 91-95

Thiol Modification By Pharmacologically Active Agents of the Diazeniumdiolate Class

Anna E. Maciag
Basic Science Program, SAIC-Frederick, Inc., Frederick, Maryland
Ryan J. Holland
Chemical Biology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, Maryland
Joseph E. Saavedra
Basic Science Program, SAIC-Frederick, Inc., Frederick, Maryland
Harinath Chakrapani
Indian Institute of Science Education and Research, Pune, India
Paul J. Shami
Division of Hematology and Hematologic Malignancies, University of Utah, Salt Lake City, Utah
Larry K. Keefer
Chemical Biology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, Maryland

RESUMO

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.