O4-ethyl-5'-dimethoxytritylthymidine-3'-(biscyanoethyl)monophosphate | 413567-58-5

• 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: O4-ethyl-5'-dimethoxytritylthymidine-3'-(biscyanoethyl)monophosphate
• 英文别名: O⁴-ethyl-5'-dimethoxytritylthymidine-3'-(biscyanoethyl)monophosphate
• CAS: 413567-58-5
• 化学式: C₃₉H₄₃N₄O₁₀P
• 分子量: 758.765
• InChiKey: OOWMYUQMRDGREA-LIVOIKKVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.62
• 重原子数：
  54.0
• 可旋转键数：
  19.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  173.38
• 氢给体数：
  0.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  O4-ethyl-5'-dimethoxytritylthymidine-3'-(biscyanoethyl)monophosphate 在 ammonium hydroxide 、 zinc dibromide 作用下， 以 硝基甲烷 为溶剂， 反应 3.0h， 生成 O⁴-ethylthymidine-3'-monophosphate
  参考文献：
  名称：

  Modified Immunoenriched ³²P-HPLC Assay for the Detection of O⁴-Ethylthymidine in Human Biomonitoring Studies

  摘要：

  Increased excretion of ethylated DNA bases has been reported in the urine of cigarette smokers. To study DNA ethylation in the target organs of smokers, an immunoenriched P-32-postlabeling assay for O-4-ethylthymidine (O-4-etT) was developed. O-4-etT-3'-monophosphate (O-4-etT-3'P) was synthesized, purified, and characterized by LC-MS, ESI-MS, and NMR. DNA was enzymatically digested to 2'-deoxynucleoside-3'-monophosphate followed by immunoprecipitation of O-4-etT-3'P using specific monoclonal antibodies. The immunoconjugate was washed by filtration, and O-4-etT-3'P was recovered by ethanol treatment. The enriched O-4-etT-3'P was labeled with [gamma-32P]ATP in the presence of T4-polynucteotide kinase at pH 6.8 to yield its 5'-labeled monophosphate and was subsequently resolved on RP-HPLC and detected with online detection of radioactivity. Adduct recovery was > 80%, and the detection limit was approximately 500 amol. To further validate the method, O-4-etT levels were determined in calf thymus DNA treated with N-etliyl-N-nitrosourea, and a dose-dependent formation of O-4-etT was observed. Furthermore, O-4-etT was found to be present in the cells obtained from the lower respiratory tract by sputum induction of two out of four smokers but not in three nonsmokers. O-4-etT is a poorly repaired promutagenic DNA lesion; thus, it could be of potential use for biomonitoring smoking-related DNA damage. Our improved assay was found to be sufficiently sensitive and specific to detect O-4-etT in surrogate cells from cigarette smoke exposed humans.

  DOI：

  10.1021/tx015582s
• 作为产物：
  描述：

  Phosphorous acid (2R,3S,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yl ester bis-(2-cyano-ethyl) ester 在 过氧化氢异丙苯 作用下， 以 甲醇 、 乙醚 、 乙腈 为溶剂， 反应 2.5h， 生成 O4-ethyl-5'-dimethoxytritylthymidine-3'-(biscyanoethyl)monophosphate
  参考文献：
  名称：

  Modified Immunoenriched ³²P-HPLC Assay for the Detection of O⁴-Ethylthymidine in Human Biomonitoring Studies

  摘要：

  Increased excretion of ethylated DNA bases has been reported in the urine of cigarette smokers. To study DNA ethylation in the target organs of smokers, an immunoenriched P-32-postlabeling assay for O-4-ethylthymidine (O-4-etT) was developed. O-4-etT-3'-monophosphate (O-4-etT-3'P) was synthesized, purified, and characterized by LC-MS, ESI-MS, and NMR. DNA was enzymatically digested to 2'-deoxynucleoside-3'-monophosphate followed by immunoprecipitation of O-4-etT-3'P using specific monoclonal antibodies. The immunoconjugate was washed by filtration, and O-4-etT-3'P was recovered by ethanol treatment. The enriched O-4-etT-3'P was labeled with [gamma-32P]ATP in the presence of T4-polynucteotide kinase at pH 6.8 to yield its 5'-labeled monophosphate and was subsequently resolved on RP-HPLC and detected with online detection of radioactivity. Adduct recovery was > 80%, and the detection limit was approximately 500 amol. To further validate the method, O-4-etT levels were determined in calf thymus DNA treated with N-etliyl-N-nitrosourea, and a dose-dependent formation of O-4-etT was observed. Furthermore, O-4-etT was found to be present in the cells obtained from the lower respiratory tract by sputum induction of two out of four smokers but not in three nonsmokers. O-4-etT is a poorly repaired promutagenic DNA lesion; thus, it could be of potential use for biomonitoring smoking-related DNA damage. Our improved assay was found to be sufficiently sensitive and specific to detect O-4-etT in surrogate cells from cigarette smoke exposed humans.

  DOI：

  10.1021/tx015582s