O⁶-[1-oxo-1-(3-pyridyl)but-4-yl]-2'deoxyguanosine | 189241-37-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: O⁶-[1-oxo-1-(3-pyridyl)but-4-yl]-2'deoxyguanosine
• 英文别名: 2'-deoxy-O⁶-[4-oxo-4-(3-pyridyl)butyl]guanosine；4-[2-amino-9-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-6-yl]oxy-1-pyridin-3-ylbutan-1-one
• CAS: 189241-37-0
• 化学式: C₁₉H₂₂N₆O₅
• 分子量: 414.421
• InChiKey: QXHUYKACECPBDJ-RRFJBIMHSA-N

物化性质

• 沸点：
  808.5±75.0 °C(Predicted)
• 密度：
  1.62±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  159
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  O⁶-[1-oxo-1-(3-pyridyl)but-4-yl]-2'deoxyguanosine 在 盐酸 作用下， 以 盐酸 为溶剂， 反应 0.5h， 生成 O⁶-[4-oxo-4-(3-pyridyl)butyl]guanine
  参考文献：
  名称：

  吡啶基氧代丁基加合物O6- [4-氧代-4-（3-吡啶基）丁基]鸟嘌呤存在于4-（乙酰氧基甲基亚氨基）-1-（3-吡啶基）-1-丁酮处理的DNA中，并且是O6-烷基鸟嘌呤的底物-DNA烷基转移酶。

  摘要：

  肺致癌物4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮（NNK）被活化为甲基化或吡啶基氧代丁基化DNA的反应性代谢产物。先前的研究表明，吡啶基氧代丁基化的DNA会干扰O6-烷基鸟嘌呤-DNA烷基转移酶（AGT）对O6-甲基鸟嘌呤（O6-mG）的修复。吡啶基氧代丁基化DNA的AGT反应性归因于（吡啶基氧代丁基）鸟嘌呤加合物。制备了一种潜在的AGT底物加合物2'-脱氧-O6- [4-氧代-4-（3-吡啶基）丁基]鸟苷（O6-pobdG）。该加合物在pH 7.0稳定超过13天，并在中性热水解条件（pH 7.0，100摄氏度，30分钟）下稳定。在温和的酸水解条件下（0.1 N HCl，80摄氏度），将O6-pobdG脱嘌呤化，以生成O6- [4-氧代-4-（3-吡啶基）丁基]鸟嘌呤（O6-pobG）。在强酸水解条件（0.8 N HCl，80摄氏度）下，O6-pobdG水解为4-羟基-1-（3-

  DOI：

  10.1021/tx9602067
• 作为产物：
  描述：

  N²,3',5'-triisobutyryl-2'-deoxyguanosine 在 silver nitrate sodium hydroxide 、 N-氯代丁二酰亚胺 、 sodium carbonate 、 三苯基膦 、 sodium sulfite 、 偶氮二甲酸二乙酯 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 21.33h， 生成 O⁶-[1-oxo-1-(3-pyridyl)but-4-yl]-2'deoxyguanosine
  参考文献：
  名称：

  吡啶基氧代丁基加合物O6- [4-氧代-4-（3-吡啶基）丁基]鸟嘌呤存在于4-（乙酰氧基甲基亚氨基）-1-（3-吡啶基）-1-丁酮处理的DNA中，并且是O6-烷基鸟嘌呤的底物-DNA烷基转移酶。

  摘要：

  肺致癌物4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮（NNK）被活化为甲基化或吡啶基氧代丁基化DNA的反应性代谢产物。先前的研究表明，吡啶基氧代丁基化的DNA会干扰O6-烷基鸟嘌呤-DNA烷基转移酶（AGT）对O6-甲基鸟嘌呤（O6-mG）的修复。吡啶基氧代丁基化DNA的AGT反应性归因于（吡啶基氧代丁基）鸟嘌呤加合物。制备了一种潜在的AGT底物加合物2'-脱氧-O6- [4-氧代-4-（3-吡啶基）丁基]鸟苷（O6-pobdG）。该加合物在pH 7.0稳定超过13天，并在中性热水解条件（pH 7.0，100摄氏度，30分钟）下稳定。在温和的酸水解条件下（0.1 N HCl，80摄氏度），将O6-pobdG脱嘌呤化，以生成O6- [4-氧代-4-（3-吡啶基）丁基]鸟嘌呤（O6-pobG）。在强酸水解条件（0.8 N HCl，80摄氏度）下，O6-pobdG水解为4-羟基-1-（3-

  DOI：

  10.1021/tx9602067

文献信息

• Identification of Adducts Produced by the Reaction of 4-(Acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanol with Deoxyguanosine and DNA
  作者：Pramod Upadhyaya、Shana J. Sturla、Natalia Tretyakova、Rebecca Ziegel、Peter W. Villalta、Mingyao Wang、Stephen S. Hecht

  DOI：10.1021/tx0256376

  日期：2003.2.1

  4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a metabolite of the tobacco specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). NNAL is present in the blood and urine of people exposed to tobacco products and has carcinogenic activity in rodents similar to that of NNK. DNA adducts specific to NNAL have not been previously identified. Metabolic activation of NNAL by a-methyl hydroxylation, a pathway known to occur in rodent and human microsomes, would produce pyridylhydroxybutylating agents that could react with DNA. We investigated this possibility in the present study by allowing 4-(acetoxymethylnitrosamino)1-(3-pyridyl)-1-butanone (NNALCH(2)OAc) to react with dGuo and DNA. Products were identified by HPLC with UV detection, liquid chromatography/electrospray ionization-mass spectrometry (LC/ESI-MS) and LC/ESI-tandem mass spectrometry (LC/ESI-MS/MS). In the dGuo reactions, selected ion monitoring for m/z 417, corresponding to pyridylhydroxybutylated dGuo, showed several peaks. One adduct was identified as 7-[1-hydroxy-1-(3-pyridyl)but-4-yl]dGuo (21) by neutral thermal hydrolysis, which converted it to 7-[1-hydroxy-1-(3-pyridyl)but-4-yl]Gua (22) and 4-hydroxy-1-(3-pyridyl)-1-butanol (16). Adduct 22 was identified by comparison of its LC/ESI-MS and LC/ESI-MS/MS properties to those of standard 22. Two other adducts, O-6-[1-hydroxy-1-(3-pyridyl)but-4-yl]dGuo (17) and N-2-[1-hydroxy-1-(3-pyridyl)but-4-yl]dGuo (19), were identified by comparison of their LC/ESI-MS and LC/ESI-MS/MS properties to those of standard 17 and 19. Further evidence for the identity of 17 and 19 was obtained by mild acid hydrolysis, which converted them to the corresponding Gua bases 18 and 20, identified by comparison to synthetic standards. Neutral thermal hydrolysis of DNA that had been reacted with NNALCH2OAc produced 22, identified by comparison to a standard. Adducts 17 and 19 were identified in enzyme hydrolysates of this DNA by comparison to standards. Thus, DNA that had been allowed to react with NNALCH(2)OAc contained adducts 17, 19, and 21. The results of this study provide markers for investigating the role of specific NNAL-DNA adducts in carcinogenesis by NNAL and NNK.
• Pyridyloxobutyl Adduct <i>O</i>⁶-[4-Oxo-4-(3-pyridyl)butyl]guanine Is Present in 4-(Acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone-Treated DNA and Is a Substrate for <i>O</i>⁶-Alkylguanine-DNA Alkyltransferase
  作者：Lijuan Wang、Thomas E. Spratt、Xiao-Keng Liu、Stephen S. Hecht、Anthony E. Pegg、Lisa A. Peterson

  DOI：10.1021/tx9602067

  日期：1997.5.1

  prepared. This adduct was stable at pH 7.0 for greater than 13 days and to neutral thermal hydrolysis conditions (pH 7.0, 100 degrees C, 30 min). Under mild acid hydrolysis conditions (0.1 N HCl, 80 degrees C), O6-pobdG was depurinated to yield O6-[4-oxo-4-(3-pyridyl)butyl]guanine (O6-pobG). O6-pobdG was hydrolyzed to 4-hydroxy-1-(3-pyridyl)-1-butanone and guanine under strong acid hydrolysis conditions

  肺致癌物4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮（NNK）被活化为甲基化或吡啶基氧代丁基化DNA的反应性代谢产物。先前的研究表明，吡啶基氧代丁基化的DNA会干扰O6-烷基鸟嘌呤-DNA烷基转移酶（AGT）对O6-甲基鸟嘌呤（O6-mG）的修复。吡啶基氧代丁基化DNA的AGT反应性归因于（吡啶基氧代丁基）鸟嘌呤加合物。制备了一种潜在的AGT底物加合物2'-脱氧-O6- [4-氧代-4-（3-吡啶基）丁基]鸟苷（O6-pobdG）。该加合物在pH 7.0稳定超过13天，并在中性热水解条件（pH 7.0，100摄氏度，30分钟）下稳定。在温和的酸水解条件下（0.1 N HCl，80摄氏度），将O6-pobdG脱嘌呤化，以生成O6- [4-氧代-4-（3-吡啶基）丁基]鸟嘌呤（O6-pobG）。在强酸水解条件（0.8 N HCl，80摄氏度）下，O6-pobdG水解为4-羟基-1-（3-