title: Dephosphorylation reactions with deferoxamine, a potential chemical nuclease.
abstract: We report a detailed kinetic and mechanistic study of the reaction of a widely used therapeutic agent, deferoxamine (DFO), which contains three nucleophilic hydroxamate groups, with the model phosphate diester bis-2,4-dinitrophenylphosphate BDNPP. We clarify the mechanism by detecting important phosphorylated intermediates in the model reaction and show that the mechanism can be extended to the reaction with DNA. The effectiveness of DFO in cleaving DNA was examined over a range of pH in the absence and presence of a biologically available metal (Zn(2+)). The results inform and complement ongoing studies involving DFO, which can act as a powerful nucleophile toward DNA and other targets susceptible to nucleophilic attack.
authors: INCT-Catálise, Departamento de Química, Universidade Federal de Santa Catarina, Campus Universitário-Trindade, 88040-900 Florianópolis, SC, Brasil.
authors: Elisa S
authors: ES
authors: Orth
authors: Michelle
authors: M
authors: Medeiros
authors: Tiago
authors: T
authors: Bortolotto
authors: Hernán
authors: H
authors: Terenzi
authors: Anthony J
authors: AJ
authors: Kirby
authors: Faruk
authors: F
authors: Nome
mesh_terms: D019297:2,4-Dinitrophenol / Q000031:analogs & derivatives* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry*; D004247:DNA / Q000378:metabolism; D053837:DNA Cleavage; D003676:Deferoxamine / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D006877:Hydroxamic Acids / Q000737:chemistry; D007502:Iron Chelating Agents / Q000737:chemistry*; D007700:Kinetics; D010755:Organophosphates / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013053:Spectrophotometry; D015032:Zinc / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D006877:Hydroxamic Acids; D007502:Iron Chelating Agents; D010755:Organophosphates; C047468:2,4-dinitrophenylphosphate; D004247:DNA; D003676:Deferoxamine; D015032:Zinc; D019297:2,4-Dinitrophenol