53-94-1Relevant articles and documents
Synthesis of site-specific damaged DNA strands by 8-(acetylarylamino)- 2′-deoxyguanosine adducts and effects on various DNA polymerases
Krueger, Sarah,Meier, Chris
, p. 1158 - 1169 (2013/04/10)
Beside the predominately found 8-(arylamino)-2′-dG, 8-(acetylarylamino) damages within DNA-strands may also play an important role in the induction of chemical carcinogenesis. A synthesis pathway leading to these 8-(acetylarylamino)-dG adducts using different aromatic amines has been optimized. The 8-modified dGs were converted into the corresponding phosphoramidites and site-specifically incorporated into different oligonucleotides leading to DNA strands. Lesion-bearing hybrids of these damaged DNA-strands with complementary oligonucleotides were used to study their melting properties and their circular dichroism spectra. It was shown that no EcoRI restriction took place with the damage inside the cleavage site. Finally, three different DNA polymerases were used for primer extension studies. C8-NAc-Arylamine adducts of 2′-deoxyguanosine with various aromatic amines were synthesized by using cross-coupling reactions and converted into 3′-phosphoramidites. Site-specific damaged NarI-, EcoRI- and 20mer-oligonucleotides were prepared by automated DNA-synthesis. Biophysical properties, restriction endonuclease studies and DNA-polymerase assays were performed. Copyright
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).
Formation and reactions of N7-aminoguanosine and derivatives
Guengerich, F. Peter,Mundkowski, Ralf G.,Voehler, Markus,Kadlubar, Fred F.
, p. 906 - 916 (2007/10/03)
Arylamines are mutagens and carcinogens and are thought to initiate tumors by forming adducts with DNA. The major adducts are C8-guanyl, and we have previously suggested a role for guanyl-N7 intermediates in the formation process. N7-Aminoguanosine (Guo) was synthesized and characterized, with the position of the NH2 at N7 established by two- dimensional rotating frame Overhauser enhancement NMR spectroscopy. In DMF, N7-NH2Guo formed C8-NH2Guo and the cyclic product C8:5'-O-cycloGuo. In aqueous media, these products were formed along with 8-oxo-7,8-dihydroGuo, N7-NH2guanine, and a product characterized as a purine 8,9-ring-opened derivative (N-aminoformamidopyrimidine). The rate of aqueous decomposition of N7-NH2Guo increased with pH, with a t( 1/2 ) of 10 h at pH 7 and a t( 1/2 ) of 2 h at pH 9. The rate of migration of NH2 from N7 to C8 is fast enough to explain the formation of C8-NH2Guo from the reaction of 2,4- dinitrophenoxyamine with Guo but not the formation of C8-(arylamino)Guo in the reaction of Guo with aryl hydroxylamine esters; however, the fluorenyl moiety may facilitate the proposed rearrangement by stabilizing an incipient negative charge in the transfer. In the reaction of Guo with N-hydroxy-2- aminofluorene and acetylsalicylic acid, a peak with the mass spectrum expected for N7-(2-aminofluorenyl)Guo was detected early in the reaction and was distinguished from C8-(2-aminofluorenyl)Guo. NMR experiments with [8- 13C]Guo also provided some additional support for transient formation of N7-(2-aminofluorenyl)Guo. We conclude that a guanyl-N7 intermediate is reasonable in the reaction of activated arylamines with nucleic acids, although an exact rate of transfer of an N7-arylamine group to the C8 position has not yet been quantified. The results provide an explanation for the numerous products associated with modification of DNA by activated arylamines. However, the contribution of 'direct' reaction at the guanine C8 atom cannot be excluded.
