5614-64-2Relevant articles and documents
Quantitation of 8-oxoguanine and strand breaks produced by four oxidizing agents
Kennedy, Laura J.,Moore Jr., Kenneth,Caulfield, Jennifer L.,Tannenbaum, Steven R.,Dedon, Peter C.
, p. 386 - 392 (1997)
Reactive oxygen species, produced endogenously or by exposure to environmental chemicals and ionizing radiation, induce a wide range of DNA lesions. The variety of chemistries associated with different oxidants suggests that each will produce a unique spectrum of DNA damage products. To extend our efforts to relate genotoxin chemistry to DNA damage, we measured both strand breaks and 8-oxoguanine (8-oxoG) in DNA after exposure to γ- radiation, Fe(II)-EDTA/H2O2, Cu(II)/H2O2, and peroxynitrite at concentrations approaching physiological relevance. We found that the ratio of 8-oxoG to strand breaks varied more than 10-fold depending on the oxidizing agent: ~0.4 for Cu(II)/H2O2 and peroxynitrite and ~0.03 for Fe(II)-EDTA/H2O2 and γ-radiation. In the case of Cu(II)/H2O2, the relative proportion of 8-oxoG and strand breaks was found to vary more than 2-fold (0.14-0.37) for different Cu(II) concentrations, consistent with other studies. We were able to detect 8-oxoG formation by peroxynitrite by using low peroxynitrite concentrations in conjunction with a sensitive immunoaffinity/HPLC-ECD methodology. The level of 8-oxoG relative to strand breaks produced by peroxynitrite was higher than that produced by Fe(II)- EDTA/H2O2 and γ-radiation, which is consistent with the altered reactivity or accessibility of a non-hydroxyl radical species produced by peroxynitrite.
Photooxidative damage of guanine in DG and DNA by the radicals derived from the α cleavage of the electronically excited carbonyl products generated in the thermolysis of alkoxymethyl-substituted dioxetanes and the photolysis of alkoxyacetones
Adam,Arnold,Saha-Moeller
, p. 597 - 604 (2001)
On thermolysis of the methoxy (MeO-TMD), tert-butoxy (tBuO-TMD), and hydroxy (HO-TMD) derivatives of 3,3,4,4-tetramethyl-1,2-dioxetane (TMD) in the presence of dG and calf-thymus DNA, the guanine is oxidized considerably more efficiently than the parent TMD. The same trend in the oxidative reactivity is observed for the photolysis of the corresponding oxy-substituted ketones versus acetone. The oxidative reactivity order in the dioxetane thermolysis, as well as in the ketone photolysis, parallels the ability of the excited ketones to release radicals (determined by spin trapping with DMPO and EPR spectroscopy) upon α cleavage (Norrish-type-I reaction). In the presence of molecular oxygen, the carbon-centered radicals are scavenged to produce peroxyl radicals, which are proposed as the reactive species in the, oxidation of the guanine in dG and calf-thymus DNA.
HETEROCYCLIC GTP CYCLOHYDROLASE 1 INHIBITORS FOR THE TREATMENT OF PAIN
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Page/Page column 68, (2011/04/19)
The present invention relates to the field of small molecule heterocyclic inhibitors of GTP cyclohydrolase (GCH-I), or a tautomer, prodrug, or pharmaceutically acceptable salt thereof. The invention also features pharmaceutical compositions of the compounds and the medical use of these compounds for the treatment or prevention of pain (e.g., inflammatory pain, nociceptive pain, functional pain, or neuropathic pain).
Regulation of one-electron oxidation rate of guanine and hole transfer rate in DNA through hydrogen bonding
Kawai, Kiyohiko,Takada, Tadao,Tojo, Sachiko,Majima, Tetsuro
, p. 8083 - 8085 (2007/10/03)
The effects of methyl and bromo groups at C5 of C on the one-electron oxidation rate of G, and on the hole transfer rate in DNA have been investigated. The rates of one-electron oxidation of G and hole transfer from Py·+ to 8-oxo-7,8-dihydrogua