7-(2-oxoheptyl)-1,N2-etheno-2'-deoxyguanosine | 423718-43-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: 7-(2-oxoheptyl)-1,N2-etheno-2'-deoxyguanosine
• 英文别名: 7-(2-oxoheptyl)-ε-dGuo；3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-(2-oxoheptyl)-4H-imidazo[1,2-a]purin-9-one
• CAS: 423718-43-8
• 化学式: C₁₉H₂₅N₅O₅
• 分子量: 403.438
• InChiKey: RIPAHXGKRMUTSP-RRFJBIMHSA-N

物化性质

• 沸点：
  810.1±75.0 °C(predicted)
• 密度：
  1.58±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  132
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  7-(2-oxoheptyl)-1,N2-etheno-2'-deoxyguanosine 在 吡啶 、 四氮唑 、 甲醇 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 8.75h， 生成 3'-O-[(N,N-diisopropylamino)-2-cyanoethoxyphosphinyl]-5'-O-(4,4'-dimethoxytrityl)-7-(2-oxoheptyl)-1,N2-etheno-2'-deoxyguanosine
  参考文献：
  名称：

  Comparison of the in Vitro Replication of the 7-(2-Oxoheptyl)-1,N²-etheno-2′-deoxyguanosine and 1,N²-Etheno-2′-deoxyguanosine Lesions by Sulfolobus solfataricus P2 DNA Polymerase IV (Dpo4)

  摘要：

  Oligonucleotides were synthesized containing the 7-(2-oxoheptyl)-etheno-dGuo adduct, which is derived from the reaction of dGuo and the lipid peroxidation product 4-oxo-2-nonenal. The in vitro replication of 7-(2-oxoheptyl)-etheno-dGuo by the model Y-family polymerase Sulfolobus solfataricus P2 DNA Polymerase IV (Dpo4) was examined in two sequences. The extension products were sequenced using an improved LC-ESI-MS/MS protocol developed in our laboratories, and the results were compared to that of the 1,N-2-etheno-dGuo adduct in the same sequence contexts. Both etheno adducts were highly miscoding when situated in 5'-TXG-3' local sequence contexts with <4% of the extension products being derived from error-free bypass. The major extension products resulted from the misinsertion of Ade opposite the adduct and a one-base deletion. The major extension products from replication of the etheno lesions in a 5'-CXG-3' local sequence context were the result of misinsertion of Ade, a one-base deletion, and error-free bypass. Other minor extension products were also identified. The 7-(2-oxoheptyl)etheno-dGuo lesion resulted in a larger frequency of misinsertion of Ade, whereas the 1,N-2-etheno-dGuo gave more of the one-base deletion product. Conformational studies of duplex DNA containing the 7-(2oxoheptyl)-etheno-dGuo in a 5'-TXG-3' sequence context by NMR indicated the presence of a pH-dependent conformational transition, likely involving the glycosyl bond at the adducted guanosine; the pK(a) for this transition was lower than that observed for the 1,N-2-epsilon-dGuo lesion. However, the 7-(2-oxoheptyl)-etheno-dGuo lesion, the complementary Cyt, and both flanking base pairs remained disordered at all pH values, which is attributed to the presence of the hydrophobic heptyl group of the 7-(2-oxoheptyl)etheno-dGuo lesion. The altered pK(a) value and the structural disorder at the 7-(2-oxoheptyl)-etheno-dGuo lesion site, as compared to the same sequence containing the 1,N-2-etheno-dGuo, may contribute to higher frequency of misinsertion of Ade.

  DOI：

  10.1021/tx100082e
• 作为产物：
  描述：

  2'-脱氧鸟苷 、 4-oxo-non-2-enal 在 potassium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.25h， 以55%的产率得到7-(2-oxoheptyl)-1,N2-etheno-2'-deoxyguanosine
  参考文献：
  名称：

  Comparison of the in Vitro Replication of the 7-(2-Oxoheptyl)-1,N²-etheno-2′-deoxyguanosine and 1,N²-Etheno-2′-deoxyguanosine Lesions by Sulfolobus solfataricus P2 DNA Polymerase IV (Dpo4)

  摘要：

  Oligonucleotides were synthesized containing the 7-(2-oxoheptyl)-etheno-dGuo adduct, which is derived from the reaction of dGuo and the lipid peroxidation product 4-oxo-2-nonenal. The in vitro replication of 7-(2-oxoheptyl)-etheno-dGuo by the model Y-family polymerase Sulfolobus solfataricus P2 DNA Polymerase IV (Dpo4) was examined in two sequences. The extension products were sequenced using an improved LC-ESI-MS/MS protocol developed in our laboratories, and the results were compared to that of the 1,N-2-etheno-dGuo adduct in the same sequence contexts. Both etheno adducts were highly miscoding when situated in 5'-TXG-3' local sequence contexts with <4% of the extension products being derived from error-free bypass. The major extension products resulted from the misinsertion of Ade opposite the adduct and a one-base deletion. The major extension products from replication of the etheno lesions in a 5'-CXG-3' local sequence context were the result of misinsertion of Ade, a one-base deletion, and error-free bypass. Other minor extension products were also identified. The 7-(2-oxoheptyl)etheno-dGuo lesion resulted in a larger frequency of misinsertion of Ade, whereas the 1,N-2-etheno-dGuo gave more of the one-base deletion product. Conformational studies of duplex DNA containing the 7-(2oxoheptyl)-etheno-dGuo in a 5'-TXG-3' sequence context by NMR indicated the presence of a pH-dependent conformational transition, likely involving the glycosyl bond at the adducted guanosine; the pK(a) for this transition was lower than that observed for the 1,N-2-epsilon-dGuo lesion. However, the 7-(2-oxoheptyl)-etheno-dGuo lesion, the complementary Cyt, and both flanking base pairs remained disordered at all pH values, which is attributed to the presence of the hydrophobic heptyl group of the 7-(2-oxoheptyl)etheno-dGuo lesion. The altered pK(a) value and the structural disorder at the 7-(2-oxoheptyl)-etheno-dGuo lesion site, as compared to the same sequence containing the 1,N-2-etheno-dGuo, may contribute to higher frequency of misinsertion of Ade.

  DOI：

  10.1021/tx100082e

文献信息

• Comparison of the in Vitro Replication of the 7-(2-Oxoheptyl)-1,<i>N</i>²-etheno-2′-deoxyguanosine and 1,<i>N</i>²-Etheno-2′-deoxyguanosine Lesions by <i>Sulfolobus solfataricus</i> P2 DNA Polymerase IV (Dpo4)
  作者：Plamen P. Christov、Katya V. Petrova、Ganesh Shanmugam、Ivan D. Kozekov、Albena Kozekova、F. Peter Guengerich、Michael P. Stone、Carmelo J. Rizzo

  DOI：10.1021/tx100082e

  日期：2010.8.16

  Oligonucleotides were synthesized containing the 7-(2-oxoheptyl)-etheno-dGuo adduct, which is derived from the reaction of dGuo and the lipid peroxidation product 4-oxo-2-nonenal. The in vitro replication of 7-(2-oxoheptyl)-etheno-dGuo by the model Y-family polymerase Sulfolobus solfataricus P2 DNA Polymerase IV (Dpo4) was examined in two sequences. The extension products were sequenced using an improved LC-ESI-MS/MS protocol developed in our laboratories, and the results were compared to that of the 1,N-2-etheno-dGuo adduct in the same sequence contexts. Both etheno adducts were highly miscoding when situated in 5'-TXG-3' local sequence contexts with <4% of the extension products being derived from error-free bypass. The major extension products resulted from the misinsertion of Ade opposite the adduct and a one-base deletion. The major extension products from replication of the etheno lesions in a 5'-CXG-3' local sequence context were the result of misinsertion of Ade, a one-base deletion, and error-free bypass. Other minor extension products were also identified. The 7-(2-oxoheptyl)etheno-dGuo lesion resulted in a larger frequency of misinsertion of Ade, whereas the 1,N-2-etheno-dGuo gave more of the one-base deletion product. Conformational studies of duplex DNA containing the 7-(2oxoheptyl)-etheno-dGuo in a 5'-TXG-3' sequence context by NMR indicated the presence of a pH-dependent conformational transition, likely involving the glycosyl bond at the adducted guanosine; the pK(a) for this transition was lower than that observed for the 1,N-2-epsilon-dGuo lesion. However, the 7-(2-oxoheptyl)-etheno-dGuo lesion, the complementary Cyt, and both flanking base pairs remained disordered at all pH values, which is attributed to the presence of the hydrophobic heptyl group of the 7-(2-oxoheptyl)etheno-dGuo lesion. The altered pK(a) value and the structural disorder at the 7-(2-oxoheptyl)-etheno-dGuo lesion site, as compared to the same sequence containing the 1,N-2-etheno-dGuo, may contribute to higher frequency of misinsertion of Ade.