Synthesis and characterization of isotopically enriched pyrimidine deoxynucleoside oxidation damage products
Synthesis and characterization of isotopically enriched pyrimidine deoxynucleoside oxidation damage products
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DOI：
10.1021/tx970186o
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发表时间：
1998-01-01
影响因子：
4.1
通讯作者：
Sowers, LC
中科院分区：
文献类型：
--
作者：
LaFrancois, CJ;Fujimoto, J;Sowers, LC
DNA的氧化损伤是基因组不稳定性的一个确定来源。在本文中，我们描述了几个嘧啶脱氧核苷氧化损伤产物的合成和表征，富含稳定同位素。这些产物包括5-（羟甲基）尿嘧啶、5-甲酰基尿嘧啶、5-羟基尿嘧啶、5-（羟甲基）胞嘧啶、5-甲酰基胞嘧啶和5-羟基胞嘧啶的2 '-脱氧核苷衍生物。常见的前体是2 '-脱氧-2“-氘[1，3-N-15]尿苷。在官能团转化过程中添加额外的稳定同位素。这些衍生物的表征包括质谱和H-1和N-15 NMR光谱。质子和氮NMR研究报告允许检查糖构象和互变异构平衡，属性可能是重要的，在理解这些DNA损伤产物的生物后果的修改的影响。
Oxidative damage to DNA is an established source of genomic instability. In this paper, we describe the synthesis and characterization of several pyrimidine deoxynucleoside oxidation damage products, enriched with stable isotopes. These products include the 2'-deoxynucleoside derivatives of 5-(hydroxymethyl)uracil, 5-formyluracil, 5-hydroxyuracil, 5-(hydroxymethyl)cytosine, 5-formylcytosine, and 5-hydroxycytosine. The common precursor is 2'-deoxy-2 "-deutero[1,3-N-15]uridine. Additional stable isotopes are added during functional group conversions. Characterization of these derivatives includes mass spectrometry and H-1 and N-15 NMR spectroscopy. Proton and nitrogen NMR studies reported here allow an examination of the influence of the modification on sugar conformation and tautomeric equilibrium, properties likely to be important in understanding the biological consequences of these DNA damage products.