N²-[1-hydroxy-1-(3-pyridyl)but-4-yl]-2'-deoxyguanosine | 502507-70-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: N²-[1-hydroxy-1-(3-pyridyl)but-4-yl]-2'-deoxyguanosine
• 英文别名: 2'-Deoxy-N-[4-hydroxy-4-(pyridin-3-yl)butyl]guanosine；9-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-[(4-hydroxy-4-pyridin-3-ylbutyl)amino]-1H-purin-6-one
• CAS: 502507-70-2
• 化学式: C₁₉H₂₄N₆O₅
• 分子量: 416.437
• InChiKey: HPPRQWBDOFYQJO-FGDMXMHKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  154
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N²-[1-hydroxy-1-(3-pyridyl)but-4-yl]-2'-deoxyguanosine 以 盐酸 为溶剂， 反应 0.5h， 以75%的产率得到N²-[1-hydroxy-1-(3-pyridyl)but-4-yl]guanine
  参考文献：
  名称：

  Identification of Adducts Produced by the Reaction of 4-(Acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanol with Deoxyguanosine and DNA

  摘要：

  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.

  DOI：

  10.1021/tx0256376
• 作为产物：
  描述：

  N²-[1-oxo-1-(3-pyridyl)but-4-yl]-2'-deoxyguanosine 在 sodium tetrahydroborate 作用下， 以 甲醇 、 acetate buffer 为溶剂， 反应 3.0h， 以75%的产率得到N²-[1-hydroxy-1-(3-pyridyl)but-4-yl]-2'-deoxyguanosine
  参考文献：
  名称：

  Identification of Adducts Produced by the Reaction of 4-(Acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanol with Deoxyguanosine and DNA

  摘要：

  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.

  DOI：

  10.1021/tx0256376