5'-O-(4,4'-dimethoxytrityl)-3'-O-toluoyl-2'-deoxyuridine | 906482-78-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 5'-O-(4,4'-dimethoxytrityl)-3'-O-toluoyl-2'-deoxyuridine
• CAS: 906482-78-8
• 化学式: C₃₈H₃₆N₂O₈
• 分子量: 648.712
• InChiKey: OAAFFQSDEGZGEZ-VUHKNJSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.38
• 重原子数：
  48.0
• 可旋转键数：
  11.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  118.08
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  5'-O-(4,4'-dimethoxytrityl)-3'-O-toluoyl-2'-deoxyuridine 在 四氮唑 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 196.0h， 生成 5'-O-(4,4'-dimethoxytrityl)-N3-(3-buten-2-O-t-butyldimethylsilyl-1-yl)-2'-deoxyuridine-3'-O-(N,N-diisopropyl-O-cyanoethyl)phosphoramidite
  参考文献：
  名称：

  Synthesis and Mutagenesis of the Butadiene-Derived N3 2‘-Deoxyuridine Adducts

  摘要：

  1,3-Butadiene is a known carcinogen and mutagen that acts through a variety of metabolic intermediates that react with DNA, forming stable and unstable lesions on dG, dA, dC, and dT. The N3 2'-deoxyuridine adducts are a highly stable, stereoisomeric mixture of adducts derived from the reaction of cytosine with the monoepoxide metabolite of butadiene, followed by spontaneous deamination. In this study, the phosphoramidites and subsequent oligodeoxynucleotides containing the N3 2'-deoxyuridine adducts have been constructed and characterized. Using a single-stranded shuttle vector DNA, the mutagenic potential of these adducts has been tested following replication in mammalian cells. Replication past the N3 2'-deoxyuridine adducts was found to be highly mutagenic with an overall mutation yield of similar to 97%. The major mutations that were observed were C to T transitions and C to A transversions. In vitro, these adducts posed a complete block to both the Klenow fragment of Escherichia coli polymerase I and polymerase epsilon, while these lesions significantly blocked polymerase delta. These data suggested a possible involvement of bypass polymerases in the in vivo replication of these lesions. Overall, these findings indicate that the N3 2'-deoxyuridine adducts are highly mutagenic lesions that may contribute to butadiene-mediated carcinogenesis.

  DOI：

  10.1021/tx060016o
• 作为产物：
  描述：

  4,4'-双甲氧基三苯甲基氯 在 吡啶 作用下， 反应 3.0h， 生成 5'-O-(4,4'-dimethoxytrityl)-3'-O-toluoyl-2'-deoxyuridine
  参考文献：
  名称：

  Synthesis and Mutagenesis of the Butadiene-Derived N3 2‘-Deoxyuridine Adducts

  摘要：

  1,3-Butadiene is a known carcinogen and mutagen that acts through a variety of metabolic intermediates that react with DNA, forming stable and unstable lesions on dG, dA, dC, and dT. The N3 2'-deoxyuridine adducts are a highly stable, stereoisomeric mixture of adducts derived from the reaction of cytosine with the monoepoxide metabolite of butadiene, followed by spontaneous deamination. In this study, the phosphoramidites and subsequent oligodeoxynucleotides containing the N3 2'-deoxyuridine adducts have been constructed and characterized. Using a single-stranded shuttle vector DNA, the mutagenic potential of these adducts has been tested following replication in mammalian cells. Replication past the N3 2'-deoxyuridine adducts was found to be highly mutagenic with an overall mutation yield of similar to 97%. The major mutations that were observed were C to T transitions and C to A transversions. In vitro, these adducts posed a complete block to both the Klenow fragment of Escherichia coli polymerase I and polymerase epsilon, while these lesions significantly blocked polymerase delta. These data suggested a possible involvement of bypass polymerases in the in vivo replication of these lesions. Overall, these findings indicate that the N3 2'-deoxyuridine adducts are highly mutagenic lesions that may contribute to butadiene-mediated carcinogenesis.

  DOI：

  10.1021/tx060016o