Photosensitized oxidation of 5-methyl-2'-deoxycytidine by 2-methyl-1,4-naphthoquinone: Characterization of 5-(hydroperoxymethyl)-2'-deoxycytidine and stable methyl group oxidation products
Photosensitized oxidation of 5-methyl-2'-deoxycytidine by 2-methyl-1,4-naphthoquinone: Characterization of 5-(hydroperoxymethyl)-2'-deoxycytidine and stable methyl group oxidation products
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DOI：
10.1021/ja962073h
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发表时间：
1996-11-20
影响因子：
15
通讯作者：
Cadet, J
中科院分区：
文献类型：
--
作者：
Bienvenu, C;Wagner, JR;Cadet, J
5-甲基胞嘧啶是真核生物DNA中的一个微小碱基，在基因表达调控中起着核心作用。5-甲基-2‘-脱氧胞苷在甲萘二酮(MQ)作为第一类光敏剂的存在下，经UV-A照射后，可生成几种稳定的氧化产物。这项研究的重点是主要分解产物的分离和表征，这些分解产物的形成涉及甲基的氧化。它们包括5-(羟甲基)-2‘-脱氧胞苷和两个稳定的分解产物，即5-(羟甲基)-2’-脱氧胞苷和5-甲酰基-2‘-脱氧胞苷。后者的结构归属是通过广泛的光谱测量(H-1和C-13核磁共振、紫外光谱和质谱学)推断出来的。此外，通过详细的H-1核磁共振分析，推测了氧化核苷的构象分析。上述所有光氧化产物似乎都是甲萘二酮光敏化生成的5-甲基-2‘-脱氧胞苷自由基阳离子的去质子化产物。
5-Methylcytosine is a minor nucleobase of eukaryotic DNA which plays a central role in the regulation of gene expression. UV-A irradiation of an aerated aqueous solution of 5-methyl-2'-deoxycytidine in the presence of menadione (MQ) as a type I photosensitizer leads to the formation of several stable oxidation products. Emphasis was placed in this study on the isolation and the characterization of the major class of decomposition products whose formation involves the oxidation of the methyl group. These include 5-(hydroperoxymethyl)-2'-deoxycytidine and two stable decomposition products namely, 5-(hydroxymethyl)-2'-deoxycytidine and 5-formyl-2'-deoxycytidine. Structural assignment df the latter modified nucleosides was inferred from extensive spectroscopic measurements (H-1 and C-13 NMR, UV spectroscopy, and mass spectrometry). In addition, conformational analysis of the oxidized nucleosides was inferred from detailed H-1 NMR analysis. All of the above photooxidation products appear to arise from the deprotonation of the 5-methyl-2'-deoxycytidine radical cation which is generated by menadione photosensitization.