methyl 3-(2-amino-6-oxo-1,6-dihydro-7H-purin-7-yl)propanoate | 1227782-47-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: methyl 3-(2-amino-6-oxo-1,6-dihydro-7H-purin-7-yl)propanoate
• CAS: 1227782-47-9
• 化学式: C₉H₁₁N₅O₃
• 分子量: 237.218
• InChiKey: VLHKJGJDBJBAQY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.74
• 重原子数：
  17.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  115.89
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  甲醇 、 7-(2'-carboxyethyl)guanine 在 乙酰氯 作用下， 生成 methyl 3-(2-amino-6-oxo-1,6-dihydro-7H-purin-7-yl)propanoate
  参考文献：
  名称：

  液相色谱-纳米电喷雾电离-高分辨率串联质谱法定量分析吸烟者和非吸烟者白细胞中甲基乙二醛和羧乙基化剂衍生的DNA加合物。

  摘要：

  建立了液相色谱-纳米电喷雾电离高分辨率串联质谱（LC-NSI-HRMS / MS）方法用于定量DNA加合物7-（2'-羧乙基）鸟嘌呤（7-2'-CEG）和N 2的方法-（1'-羧乙基）鸟嘌呤（N 2 -1'-CEG），作为它们的甲酯，存在于吸烟者和非吸烟者的人白细胞DNA中。先前已在所有分析的人类肝脏样品中鉴定出7-2'-CEG，它由未知的羧乙基化剂形成，而N 2-1'-CEG由晚期糖基化终产物甲基乙二醛形成。该方法用于分析来自20位吸烟者和20位非吸烟者的白细胞DNA中的这两种DNA加合物，部分目的是为了验证以下假设：如先前在治疗的大鼠中观察到的，内源性亚硝化可形成7-2'-CEG与亚硝基二氢尿嘧啶和亚硝酸盐。吸烟者的7-2'-CEG水平（平均值±SD）为0.6±0.2 pmol /μmoldG，非吸烟者为0.5±0.2 pmol /μmoldG，而N 2-1'-CEG在吸烟者中为4.5±1

  DOI：

  10.1016/j.cbi.2020.109140

文献信息

• Detection of 7-(2′-Carboxyethyl)guanine but Not 7-Carboxymethylguanine in Human Liver DNA
  作者：Guang Cheng、Mingyao Wang、Peter W. Villalta、Stephen S. Hecht

  DOI：10.1021/tx100062v

  日期：2010.6.21

  7-Carboxymethylguanine (7-CMGua) and 7-(2'-carboxyethyl)guanine (7-CEGua) are DNA adducts that potentially could be formed upon the metabolism of the carcinogenic nitrosamines N-nitrososarcosine (NSAR) and 3-(methylnitrosamino)propionic acid (MNPA), respectively, or from other sources such as nitrosation of glycine (7-CMGua) or reaction of DNA with acrylic acid (7-CEGua). Since both NSAR and MNPA have been detected in human urine and there are plausible sources of exposure to other precursors to these adducts, we analyzed human liver DNA for 7-CMGua and 7-CEGua, using liquid chromatography-electrospray ionization-tandem mass spectrometry-selected reaction monitoring (LC-ESI-MS/MS-SRM). Human hepatic DNA was mixed with [N-15(5)]7-CMGua and [N-15(5)]7-CEGua as internal standards and enzymatically hydrolyzed. The hydrolysate was partially purified by solid-phase extraction, and the resulting fraction was treated with acetyl chloride in methanol to convert 7-CMGua and 7-CEGua to their methyl esters. After a second solid-phase extraction, LC-ESI-MS/MS-SRM analysis was carried out using the transitions m/z 224 [M + H](+) -> m/z 164 [(M + H) - HCOOCH3](+) and m/z 238 [M + H](+) -> m/z 152 [BH](+) for the methyl esters of 7-CMGua and 7-CEGua, respectively. The method was sensitive, accurate, precise, and apparently free from artifact formation. 7-CEGua, as its methyl ester, was detected in all 24 human liver samples analyzed, mean +/- SD, 373 +/- 320 fmol/mu mol Gua (74.6 adducts per 10(9) nucleotides), range 17-1189 fmol/mu mol Gua, but the methyl ester of 7-CMGua was not detected in any sample. These results demonstrate the ubiquitous presence of 7-CEGua in human liver DNA. Acrylic acid may be a likely endogenous precursor to 7-CEGua.