2R,3R-1,4-bis(2'-deoxyadenosin-N⁶-yl)butane-2,3-diol

• 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: 2R,3R-1,4-bis(2'-deoxyadenosin-N⁶-yl)butane-2,3-diol
• 英文别名: (2R,3R)-1,4-bis[[9-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-6-yl]amino]butane-2,3-diol
• 化学式: C₂₄H₃₂N₁₀O₈
• 分子量: 588.58
• InChiKey: XGEFBVGRHLLWKP-OVSMWIARSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  42
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  251
• 氢给体数：
  8
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  6-chloropurine-2'-deoxyriboside 、 2R,3R-1,4-diamino-2,3-butanediol 在 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 5.0h， 以75%的产率得到2R,3R-1,4-bis(2'-deoxyadenosin-N⁶-yl)butane-2,3-diol
  参考文献：
  名称：

  Mutagenic Spectrum of Butadiene-Derived N1-Deoxyinosine Adducts and N⁶,N⁶-Deoxyadenosine Intrastrand Cross-Links in Mammalian Cells

  摘要：

  Reactive metabolites of 1,3-butadiene, including 1,2-epoxy-3-butene (BDO), 1,2:3,4-diepoxybutane (BDO2), and 3,4-epoxy-1,2-butanediol (BDE), form both stable and unstable base adducts in DNA and have been implicated in producing genotoxic effects in rodents and human cells. N1 deoxyadenosine adducts are unstable and can undergo either hydrolytic deamination to yield N1 deoxyinosine adducts or Dimroth rearrangement to yield N-6 adducts. The dominant point mutation observed at AT sites in both in vivo and in vitro mutagenesis studies using BD and its epoxides has been A --> T transversions followed by A --> G transitions. To understand which of the butadiene adducts are responsible for mutations at AT sites, the present study focuses on the N1 deoxyinosine adduct at C2 of BDO and N-6,N-6-deoxyadenosine intrastrand cross-links derived from BDO2. These lesions were incorporated site-specifically and stereospecifically into oligodeoxynucleotides which were engineered into mammalian shuttle vectors for replication bypass and mutational analyses in COS-7 cells. Replication of DNAs containing the R,R-BDO2 intrastrand cross-link between N-6 positions of deoxyadenosine yielded a high frequency (59%) of single base substitutions at the 3' adducted base, while 19% mutagenesis was detected using the S,S-diastereomer. Comparable studies using the R- and S-diastereomers of the N1 deoxyinosine adduct gave rise to similar to50 and 80% A --> G transitions with overall mutagenic frequencies of 59 and 90%, respectively. Collectively, these data establish a molecular basis for A --> G transitions that are observed following in vivo and in vitro exposures to 131) and its epoxides, but fail to reveal the source of the A --> T transversions that are the dominant point mutation.

  DOI：

  10.1021/tx025591g

文献信息

• Mutagenic Spectrum of Butadiene-Derived <i>N</i>1-Deoxyinosine Adducts and <i>N</i>⁶,<i>N</i>⁶-Deoxyadenosine Intrastrand Cross-Links in Mammalian Cells
  作者：Manorama Kanuri、Lubomir V. Nechev、Pamela J. Tamura、Constance M. Harris、Thomas M. Harris、R. Stephen Lloyd

  DOI：10.1021/tx025591g

  日期：2002.12.1

  Reactive metabolites of 1,3-butadiene, including 1,2-epoxy-3-butene (BDO), 1,2:3,4-diepoxybutane (BDO2), and 3,4-epoxy-1,2-butanediol (BDE), form both stable and unstable base adducts in DNA and have been implicated in producing genotoxic effects in rodents and human cells. N1 deoxyadenosine adducts are unstable and can undergo either hydrolytic deamination to yield N1 deoxyinosine adducts or Dimroth rearrangement to yield N-6 adducts. The dominant point mutation observed at AT sites in both in vivo and in vitro mutagenesis studies using BD and its epoxides has been A --> T transversions followed by A --> G transitions. To understand which of the butadiene adducts are responsible for mutations at AT sites, the present study focuses on the N1 deoxyinosine adduct at C2 of BDO and N-6,N-6-deoxyadenosine intrastrand cross-links derived from BDO2. These lesions were incorporated site-specifically and stereospecifically into oligodeoxynucleotides which were engineered into mammalian shuttle vectors for replication bypass and mutational analyses in COS-7 cells. Replication of DNAs containing the R,R-BDO2 intrastrand cross-link between N-6 positions of deoxyadenosine yielded a high frequency (59%) of single base substitutions at the 3' adducted base, while 19% mutagenesis was detected using the S,S-diastereomer. Comparable studies using the R- and S-diastereomers of the N1 deoxyinosine adduct gave rise to similar to50 and 80% A --> G transitions with overall mutagenic frequencies of 59 and 90%, respectively. Collectively, these data establish a molecular basis for A --> G transitions that are observed following in vivo and in vitro exposures to 131) and its epoxides, but fail to reveal the source of the A --> T transversions that are the dominant point mutation.