N-(3'-monophosphate-2'-deoxyguanosin-8-yl)-4-methylaniline | 182230-62-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: N-(3'-monophosphate-2'-deoxyguanosin-8-yl)-4-methylaniline
• CAS: 182230-62-2
• 化学式: C₁₇H₂₁N₆O₇P
• 分子量: 452.363
• InChiKey: AZUKPZJUMLYJJH-QJPTWQEYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.51
• 重原子数：
  31.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  197.84
• 氢给体数：
  6.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  N-(3'-monophosphate-2'-deoxyguanosin-8-yl)-4-methylaniline 在 T₄ polynucleotide kinase 、 spermidine buffer 、 5’-三磷酸腺苷 作用下， 以 水 为溶剂， 生成
  参考文献：
  名称：

  N-（脱氧鸟苷-8-基）芳胺加合物的32P后标记：标记效率的比较研究。

  摘要：

  32P后标记是检测DNA加合物的一种非常强大的技术。通常，通过（32）P-后标记对DNA加合物的定量是通过相对加合物标记来实现的，方法是将加合物中掺入的放射性与正常核苷酸相关的放射性进行比较。该方法基于许多假设，最重要的是将正常的和加成的核苷酸3'-磷酸酯以相似的效率转化为3'，5'-双磷酸酯。为了评估特定DNA加合物的标记效率，我们对T（4）多核苷酸激酶使用2'-脱氧鸟苷3'-磷酸（dG3'p）和一系列N-（deoxyguanosin-8 -基）芳基胺3'-磷酸加合物标准品（dG3'p-C8-Ar，Ar为4-氨基联苯，3-和4-甲基苯胺，以及2,4-和3,4-二甲基苯胺）。dG3'p和dG3'p-C8-Ar加合物的磷酸化遵循Michaelis-Menten动力学。与标记dG3'p相比，标记dG3'p-C8-Ar加合物时的表观营业额低40-240倍。计算的dG3'p-C8-4-氨基联苯的表观特异性常数（1

  DOI：

  10.1021/tx990038t
• 作为产物：
  描述：

  N-(对甲苯基)羟胺 在 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 水 为溶剂， 反应 3.0h， 生成 N-(3'-monophosphate-2'-deoxyguanosin-8-yl)-4-methylaniline
  参考文献：
  名称：

  Synthesis and Quantification of DNA Adducts of 4,4‘-Methylenedianiline

  摘要：

  4,4'-Methylenedianiline (MDA) is used as a hardener in the manufacture of plastics and polyurethanes. MDA has been classified as a carcinogen in animals and is a suspected human carcinogen. Assuming that MDA would yield similar DNA adducts to other arylamines, we synthesized the following C-8 guanine adducts: N'-acetyl-N-(deoxyguanosin-8-yl)-MDA, N-(deoxyguanosin-8-yl)-MDA, N-(deoxyguanosin-8-yl)-4MA, and their corresponding 3'-monophosphate derivatives. We developed methods to identify these adducts of MDA in liver DNA using P-32-postlabeling, HPLC, and GC-MS techniques. Liver DNA was obtained from rats treated with radiolabeled MDA (1.11 and 116.5 mu mol/kg body weight). The total radioactivity bound to the DNA corresponded to 0.06 and 2.7 adducts per 10(7) nucleotides [covalent binding index (CBI=(mu mol of adduct per mol of nucleotide)/(mmol of compound per kg body weight)) of 1.05 and 2.3]. This DNA-binding potency is in the range of weakly genotoxic compounds. The liver DNA was analyzed for the presence of the synthesized adducts by the following methods: (I) HPLC analysis of nucleotides and purines after enzymatic and acid hydrolysis, and (II) P-32-postlabeling after enzymatic hydrolysis. The major adducts found in vivo did not correspond to the synthesized standards. Further work was carried out to determine the structure of the unidentified adducts. It was possible to release MDA and MDA-d(4) from DNA of rats dosed with MDA and/or MDA-d(4) and from the synthesized adducts using strong base hydrolysis. Liver of two female Wistar rats given 500 mu mol/kg MDA . 2HCl was hydrolyzed in 0.1 M NaOH overnight at 110 degrees C. GC-MS analysis of the heptafluorobutyric anhydride derivatized dichloromethane extracts detected 428+/-40 fmol of MDA/mg of DNA. In the control animals no MDA was found. The experiment was repeated with livers from animals dosed 500 mu mol/kg MDA-d(4) . 2HCl. In these rats 488+/-19 fmol MDA-d(4) was found to be bound at liver DNA. Taking into account a 68% yield of the method, the CBI found in these cases was 0.82 and 1.0, respectively.

  DOI：

  10.1021/tx950194+

文献信息

• Synthesis, Characterization, and Conformational Analysis of DNA Adducts from Methylated Anilines Present in Tobacco Smoke
  作者：M. Matilde Marques、Luísa L. G. Mourato、M. Amélia Santos、Frederick A. Beland

  DOI：10.1021/tx950044z

  日期：1996.1.1

  to the arylamine nitrogen had a higher percentage of syn conformers. This observation was supported by theoretical simulation studies that indicated substantial percentages of low energy syn conformers, increasing with the substitution pattern in the order para < meta < ortho < ortho,para < ortho,meta. The results demonstrate that, although single-ring arylamines are considered weak carcinogens, their

  烟草烟雾中存在的一系列芳香胺（2-，3-和4-甲基苯胺，2,3-和2,4-二甲基苯胺）与DNA结合的能力已通过N-（酰氧基）芳基胺的反应进行了研究带有dG，dG核苷酸和DNA。通过光谱法和HPLC法将与dG和核苷酸反应的主要产物表征为N-（脱氧鸟苷-8-基）芳基胺。修饰DNA的HPLC和光谱分析表明相同的加合物。1 H和13 C NMR光谱的分析表明，含有在芳基胺氮上邻位的甲基取代基的加合物具有较高百分比的顺式构象异构体。这一观察结果得到理论模拟研究的支持，该研究表明低能同构异构体的百分比很高，并且随着取代模式的增加，其对位