Preparation of nucleotide advanced glycation endproducts--imidazopurinone adducts formed by glycation of deoxyguanosine with glyoxal and methylglyoxal.

Preparation of nucleotide advanced glycation endproducts--imidazopurinone adducts formed by glycation of deoxyguanosine with glyoxal and methylglyoxal.
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DOI:
10.1196/annals.1433.037
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发表时间:
2008-04
影响因子:
5.2
通讯作者:
Thornalley PJ
Thornalley PJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Fleming T;Rabbani N;Thornalley PJ

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An analytical procedure was developed for nucleotide advanced glycation endproducts formed by the reaction of glyoxal and methylglyoxal with deoxyguanosine under physiological conditions. For this, the imidazopurinone derivatives, 3-(2′-deoxyribosyl)-6,7-dihydro-6,7-dihydroxyimidazo[2,3-b]purin-9(8)one (dG-G) and 3-(2′-deoxyribosyl)-6,7-dihydro-6,7-dihydroxy-6-methylimidazo-[2,3-b]purine-9(8)one (dG-MG), were prepared. Authentic standard and stable isotope-substituted standard adducts were prepared and an isotopic dilution analysis assay methodology was developed using liquid chromatography with tandem mass spectrometry and optimized DNA extraction and nuclease digestion procedures. Analysis of dG-G, dG-MG, and the oxidative marker 8-hydroxydeoxyguanosine in the DNA of cultured human cells and mononuclear leukocytes showed that nucleotide advanced glycation endproducts are major markers of DNA damage in human cells.
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