73051-69-1Relevant articles and documents
Screening for reactive metabolites using electro-optical arrays featuring human liver cytosol and microsomal enzyme sources and DNA
Zhao, Linlin,Schenkman, John B.,Rusling, James F.
, p. 5386 - 5388 (2009)
We demonstrate for the first time the combination of human liver cytosol and microsomal enzyme sources into an electro-optical array to screen for reactive metabolites produced in multi-enzyme metabolic processes. The Royal Society of Chemistry 2009.
Spectroscopic characterization of the initial C8 intermediate in the reaction of the 2-fluorenylnitrenium ion with 2'-deoxyguanosine
McClelland, Robert A.,Ahmad, Abid,Dicks, Andrew P.,Licence, Victoria E.
, p. 3303 - 3310 (1999)
Irradiation of 2-azidofluorene in an aqueous solution containing 2'- deoxyguanosine (dG) gives good yields of 8-(2-fluorenylamino)dG. This is the C8 adduct implicated in the carcinogenicity of 2-aminofluorene, and formed in vivo from the reaction of DNA-guanine and an ester of N-hydroxy-2- aminofluorene. Flash photolysis of the azide reveals two intermediates on the pathway that forms this adduct, the 2-fluorenylnitrenium ion, and a subsequent longer-lived species formed in the reaction of this ion with dG. A number of pieces of evidence identify this later intermediate as the initial C8 adduct derived from addition of the nitrenium ion to the C8 carbon prior to loss of the C8 proton. Both spectroscopic and kinetic analyses show that the latter actually exists in both a cationic acid form and a base form, with a pK(a) for the acid of 3.9. The base form is a tautomer of the final product and is the species present at pH 7. There is also evidence that the reaction of the nitrenium ion and dG that forms this intermediate proceeds directly by addition at C8. In other words, the substitution of ArNH+ for H+ at the C8 position of 2'-deoxyguanosine is a straightforward electrophilic aromatic substitution.
Synthesis of DNA strands site-specifically damaged by C8-arylamine purine adducts and effects on various DNA polymerases
Boege, Nicolas,Jacobsen, Maike I.,Szombati, Zita,Baerns, Sabrina,Di Pasquale, Francesca,Marx, Andreas,Meier, Chris
experimental part, p. 11194 - 11208 (2009/11/30)
C8-Arylamine-dG and C8-arylamine-dA adducts have been prepared using palladium cross-coupling chemistry. These adducts were subsequently converted into the corresponding 5′-O-DMTr-C8-arylamine-3′-O-phosphoramidites and then used for the automated synthesi
Synthesis of DNA-oligonucleotides damaged by arylamine-modified 2′-deoxyguanosine
Boege,Szombati,Meier
, p. 705 - 708 (2008/09/17)
C8-Arylamine-dG adducts bearing a labile N-formamidine group at the exocyclic amino function were converted into their corresponding 5′-O-DMTr-3′-O-phosphoramidite-C8-arylamine-dG derivatives. These compounds were used for the automated synthesis of site-
Site-specific synthesis and properties of oligonucleotides containing C8-deoxyguanosine adducts of the dietary mutagen IQ
Elmquist, C. Eric,Stover, James S.,Wang, Zhiwei,Rizzo, Carmelo J.
, p. 11189 - 11201 (2007/10/03)
The site-specific synthesis of oligonucleotides containing the C8-deoxyguanosine adduct of the highly mutagenic heterocyclic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) has been achieved, and the oligonucleotides were characterized by UV melting te
A practical approach for the chemical synthesis of 2′-deoxyguanosine-C8 adducts with mutagenic/carcinogenic amino- or nitro-arenes
Takamura-Enya, Takeji,Ishikawa, Satoko,Mochizuki, Masataka,Wakabayashi, Keiji
, p. 5969 - 5973 (2007/10/03)
Synthetic methods for the preparation of 2′-deoxyguanosine-C8 (dG-C8) adducts with several mutagenic and carcinogenic amino- or nitro-arenes were developed using the palladium-mediated cross-coupling reaction of protected 8-amino-dG with bromoarenes in ar
Preparation of C8-amine and acetylamine adducts of 2′-deoxyguanosine suitably protected for DNA synthesis
Gillet, Ludovic C. J.,Schaerer, Orlando D.
, p. 4205 - 4208 (2007/10/03)
(Equation presented) C8-Amine and acetylamine adducts of 2′-deoxyguanosine were synthesized. Our approach provides solutions for the coupling of aromatic amines to a protected 8-bromo-2′-deoxyguanosine derivative, for the selective acetylation of the coup
Reaction of arylnitrenium ions with guanine derivatives: N1-methylguanosine and N2,N2-dimethylguanosine
Cheng, Bernice,McClelland, Robert A.
, p. 1881 - 1886 (2007/10/03)
A prior flash photolysis study of the direct reaction of arylnitrenium ions with 2′-deoxyguanosine identified a second intermediate that grew in as the transient nitrenium ion reacted with the nucleoside. This intermediate was identified as the the product of the addition of the nitrenium ion to the C-8 position of guanine prior to loss of the C-8 proton - the C-8 intermediate. A feature of the C-8 intermediate is that it exists in acid-base forms. This behavior was evident in both a spectroscopic analysis as well as in the rate-pH profile, which showed a break around pH 4 from a pH-independent reaction to a reaction that was first-order in H+. The present study was designed to identify the structure of the conjugate base form. This involved a kinetic study of the decay of the C-8 intermediate derived from the reaction of the 2-fluorenylnitrenium ion with N1-methylguanosine and N2,N2-dimethylguanosine. The rationale was that the former is unable to lose the N-1 proton, while the latter cannot deprotonate at the NH2 group. The rate-pH profiles clearly show that it is the N-1 proton that is acidic. The rate constants for the C-8 intermediate of N2,N2-dimethylguanosine show the same downward break observed with 2′-deoxyguanosine and guanosine associated with conversion to the conjugate base form. In contrast, the rate constants for the N1-methylguanosine intermediate are independent of pH. Rate constants for the reaction forming the C-8 intermediate are also reported. These show that the reaction of nitrenium ions with the N2,N2-dimethylguanine derivative is significantly faster (except where the reactions are diffusion controlled). This is consistent with the initial step of the reaction of an arylnitrenium ion and guanine occurring by direct addition at C-8. The developing positive charge in such a reaction can be delocalized to the C-2 position where π donors such as NH2 and NMe2 can exert a stabilizing effect.
Synthesis of N-acetoxy-N-benzoyl-2-aminofluorene, an ultimate carcinogen by LTA oxidation of α-phenyl-N-(2-aminofluorenyl)nitrone, and N-(2′-deoxyguanosin-8-yl)-2-aminofluorene
Mallesha,Ravi Kumar,Rangappa
, p. 2415 - 2418 (2007/10/03)
The rearrangement of a new α-phenyl-N-(2-aminofluorenyl)nitrone (8) to a new ultimate carcinogen, N-acetoxy-N-benzoyl-2-aminofluorene (9) is achieved in a lead tetraacetate (LTA) oxidation reaction. Compound 9 reacts with deoxyguanosine (dG) at pH 7.0 to give N-(benzoyl)-N-(deoxyguanosin-8-yl)-2-aminofluorene (10). Subsequent debenzoylation with the heterogeneous system (sodium carbonate/methanol) leads to the C8-adduct, N-(2′-deoxyguanosin-8-yl)-2-aminofluorene (11).
