8-[2-(trimethylsilyl)ethylthio]-2'-deoxyinosine | 1346653-28-8

• 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: 8-[2-(trimethylsilyl)ethylthio]-2'-deoxyinosine
• CAS: 1346653-28-8
• 化学式: C₁₅H₂₄N₄O₄SSi
• 分子量: 384.531
• InChiKey: QWSFAOZHKFDDDO-HBNTYKKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  25.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  113.52
• 氢给体数：
  3.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  8-[2-(trimethylsilyl)ethylthio]-2'-deoxyinosine 在 四丁基氟化铵 作用下， 反应 0.42h， 以45%的产率得到8-thio-2’-deoxyinosine
  参考文献：
  名称：

  Insights into the substrate specificity of the MutT pyrophosphohydrolase using structural analogues of 8-oxo-2′-deoxyguanosine nucleotide

  摘要：

  The bacterial repair enzyme MutT hydrolyzes the damaged nucleotide OdGTP (the 5'-triphosphate derivative of 8-oxo-2'-deoxyguanosine; OdG), which is a known mutagen and has been linked to antibacterial action. Previous work has indicated important roles for the C8-oxygen, N7-hydrogen, and C2-exo-cyclic amine during OdGTP recognition by MutT. In order to gain a more nuanced understanding of the contribution of these three sites to the overall activity of MutT, we determined the reaction parameters for dGTP, OdGTP, and nine of their analogues using steady state kinetics. Our results indicate that overall high reaction efficiencies can be achieved despite altering any one of these sites. However, altering two or more sites leads to a significant decrease in efficiency. The data also suggest that, similar to another bacterial OdG repair enzyme, MutM, a specific carbonyl in the enzyme can not only promote activity by forming an active site hydrogen bond with the N7-hydrogen of OdGTP, but can also hinder activity through electrostatic repulsion with the N7-lone pair of dGTP. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.02.083
• 作为产物：
  描述：

  2-(三甲基硅烷)乙硫醇 、 8-bromo-2'-deoxyinosine 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 以38%的产率得到8-[2-(trimethylsilyl)ethylthio]-2'-deoxyinosine
  参考文献：
  名称：

  Importance of the C2, N7, and C8 Positions to the Mutagenic Potential of 8-Oxo-2′-deoxyguanosine with Two A Family Polymerases

  摘要：

  8-Oxo-2'-deoxyguanosine (OdG) is a prominent DNA lesion produced from the reaction of 2'-deoxyguanosine (dG) with reactive oxygen species. While dG directs the insertion of only dCTP during replication, OdG can direct the insertion of either dCTP or dATP, allowing for the production of dG -> dT transversions. When replicated by Klenow fragment-exo (KF-exo), OdG preferentially directs the incorporation of dCTP over dATP, thus decreasing its mutagenic potential. However, when replicated by a highly related polymerase, the large fragment of polymerase I from Bacillus stearothermophilus (BF), dATP incorporation is preferred, and a higher mutagenic potential results. To gain insight into the reasons for this opposite preference and the effects of the C2, N7, and C8 positions on OdG mutagenicity, single-nucleotide insertions of dCTP and/or dATP opposite dG, OdG, and seven of their analogues were examined by steady state kinetics with both KF-exo and BF. Results from these studies suggest that the two enzymes behave similarly and are both sensitive not only to steric and electronic changes within the imidazole ring during both dCTP and dATP incorporation but also to the presence of the C2-exocyclic amine during dATP incorporation. The difference in incorporation preference opposite OdG appears to be due to a somewhat increased sensitivity to structural perturbations during dCTP incorporation with BF. Single-nucleotide extensions past the resulting base pairs were also studied and were not only similar between the two enzymes but also consistent with published ternary crystallographic studies with BF. These results are analyzed in the context of previous biochemical and structural studies, as well as stability studies with the resulting base pairs.

  DOI：

  10.1021/bi201383c