8-(2-(trimethylsilyl)ethyl)thio-2’-deoxyguanosine | 794574-97-3

• 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)ethyl)thio-2’-deoxyguanosine
• 英文别名: 8-(2-(trimethylsilyl)ethyl)thio-2'-deoxyguanosine；Guanosine, 2a(2)-deoxy-8-[[2-(trimethylsilyl)ethyl]thio]-；2-amino-9-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-8-(2-trimethylsilylethylsulfanyl)-1H-purin-6-one
• CAS: 794574-97-3
• 化学式: C₁₅H₂₅N₅O₄SSi
• 分子量: 399.546
• InChiKey: CTABUGCFLHMSAQ-IVZWLZJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.77
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  160
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  8-(2-(trimethylsilyl)ethyl)thio-2’-deoxyguanosine 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 7.83h， 生成 3’-O-(acetyl)-N²-(N,N-dimethylaminomethyliden)-8-(2-(trimethylsilyl)ethyl)thio-2’-deoxyguanosine
  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-溴-2'-脱氧鸟苷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 以63%的产率得到8-(2-(trimethylsilyl)ethyl)thio-2’-deoxyguanosine
  参考文献：
  名称：

  Oligonucleotide Incorporation of 8-Thio-2‘-deoxyguanosine

  摘要：

  (GRAPHICS)8-Thio-2'-deoxyguanosine (SdG) is a useful analogue of the abundant promutagen 8-oxo-2'-deoxyguanosine (OdG). Its synthesis and DNA incorporation using standard phosphoramidite chemistry is reported. To prevent oxidation during DNA synthesis, the sulfur was protected as a 2-(trimethylsilyl)ethyl sulfide. Subsequent treatment with TBAF yielded the desired 8-thiocarbonyl functionality. Melting studies with SdG revealed almost equal stabilities of SdG:dC and SdG:dA base pairs, lending insight into the base-pairing preferences of OdG.

  DOI：

  10.1021/ol0484097

文献信息

• Insights into the substrate specificity of the MutT pyrophosphohydrolase using structural analogues of 8-oxo-2′-deoxyguanosine nucleotide
  作者：Michelle L. Hamm、Emily J. McFadden、Michael Ghio、Maria A.M. Lindell、Kenneth S. Gerien、Suzanne F. O’Handley

  DOI：10.1016/j.bmcl.2016.02.083

  日期：2016.4

  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.
• Oligonucleotide Incorporation of 8-Thio-2‘-deoxyguanosine
  作者：Michelle L. Hamm、Rushina Cholera、Courtney L. Hoey、Timothy J. Gill

  DOI：10.1021/ol0484097

  日期：2004.10.1

  (GRAPHICS)8-Thio-2'-deoxyguanosine (SdG) is a useful analogue of the abundant promutagen 8-oxo-2'-deoxyguanosine (OdG). Its synthesis and DNA incorporation using standard phosphoramidite chemistry is reported. To prevent oxidation during DNA synthesis, the sulfur was protected as a 2-(trimethylsilyl)ethyl sulfide. Subsequent treatment with TBAF yielded the desired 8-thiocarbonyl functionality. Melting studies with SdG revealed almost equal stabilities of SdG:dC and SdG:dA base pairs, lending insight into the base-pairing preferences of OdG.