Pluskota-Karwatka Donata, Pawłowicz Agnieszka J, Tomas Magdalena, Kronberg Leif
Faculty of Chemistry, Adam Mickiewicz University, Grunwaldzka 6, 60-780 Poznań, Poland.
Bioorg Chem. 2008 Apr;36(2):57-64. doi: 10.1016/j.bioorg.2007.10.004. Epub 2007 Dec 19.
The reactions of glyoxal with 2'-deoxyguanosine and calf thymus single- and double-stranded DNA in aqueous buffered solutions at physiological conditions resulted in the formation of two previously undetected adducts in addition to the known reaction product 3-(2'-deoxy-beta-D-erythro-pentofuranosyl)-5,6,7-trihydro-6,7-dihydroxyimidazo[1,2-a]purine-9-one (Gx-dG). The adducts were isolated and purified by reversed-phase liquid chromatography and structurally characterised by UV absorbance, mass spectrometry, (1)H and (13)C NMR spectroscopy. The hitherto unknown adducts were identified as: 5-carboxymethyl-3-(2'-deoxy-beta-D-erythro-pentofuranosyl)-5,6,7-trihydro-6,7-dihydroxyimidazo[1,2-a]purine-9-one (Gx(2)-dG) and N(2)-(carboxymethyl)-9-(2'-deoxy-beta-D-erythro-pentofuranosyl)-purin-6(9H)-one (Gx(1)-dG). Both adducts were shown to arise from Gx-dG. Gx-dG and Gx(2)-dG were found to be unstable and partly transformed to Gx(1)-dG, which is a stable adduct and seems to be the end-product of the glyoxal reaction with 2'-deoxyguanosine. All adducts formed in the reaction of glyoxal with 2'-deoxyguanosine were observed in calf thymus DNA. Also in DNA, Gx(1)-dG was the only stable adduct. The transformation of Gx-dG to Gx(1)-dG seemed to take place in single-stranded DNA and therefore, Gx(1)-dG may be a potentially reliable biomarker for glyoxal exposure and may be involved in the genotoxic properties of the compound.
在生理条件下的水性缓冲溶液中，乙二醛与2'-脱氧鸟苷以及小牛胸腺单链和双链DNA的反应，除了已知的反应产物3-(2'-脱氧-β-D-赤藓糖基)-5,6,7-三氢-6,7-二羟基咪唑并[1,2-a]嘌呤-9-酮（Gx-dG）外，还生成了两种先前未检测到的加合物。通过反相液相色谱法分离并纯化了这些加合物，并通过紫外吸收、质谱、(1)H和(13)C核磁共振光谱对其结构进行了表征。迄今未知的加合物被鉴定为：5-羧甲基-3-(2'-脱氧-β-D-赤藓糖基)-5,6,7-三氢-6,7-二羟基咪唑并[1,2-a]嘌呤-9-酮（Gx(2)-dG）和N(2)-(羧甲基)-9-(2'-脱氧-β-D-赤藓糖基)-嘌呤-6(9H)-酮（Gx(1)-dG）。两种加合物均显示由Gx-dG产生。发现Gx-dG和Gx(2)-dG不稳定，部分转化为Gx(1)-dG，Gx(1)-dG是一种稳定的加合物，似乎是乙二醛与2'-脱氧鸟苷反应的终产物。在乙二醛与2'-脱氧鸟苷反应中形成的所有加合物在小牛胸腺DNA中均有观察到。在DNA中也是如此，Gx(1)-dG是唯一稳定的加合物。Gx-dG向Gx(1)-dG的转化似乎发生在单链DNA中，因此，Gx(1)-dG可能是乙二醛暴露的潜在可靠生物标志物，并且可能与该化合物的遗传毒性特性有关。
