5'-dimethoxytritylthymidine-3'-(biscyanoethyl)monophosphate | 76759-76-7

• 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'-dimethoxytritylthymidine-3'-(biscyanoethyl)monophosphate
• 英文别名: 5'-O-(4,4'-dimethoxytrityl)thymidine-3'-bis(2-cyanoethyl)phosphate；[(2R,3S,5R)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl] bis(2-cyanoethyl) phosphate
• CAS: 76759-76-7
• 化学式: C₃₇H₃₉N₄O₁₀P
• 分子量: 730.711
• InChiKey: SMZUQGCOVXJNGY-LBFZIJHGSA-N

物化性质

• 密度：
  1.36±0.1 g/cm3(Predicted)
• 溶解度：
  甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  5.51
• 重原子数：
  52.0
• 可旋转键数：
  17.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  184.12
• 氢给体数：
  1.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  5'-dimethoxytritylthymidine-3'-(biscyanoethyl)monophosphate 在 ammonium hydroxide 、 nuclease P₁ 、 T₄ kinase 、 DTT 、 溶剂黄146 、 5’-三磷酸腺苷 、 magnesium chloride 作用下， 以 水 为溶剂， 反应 0.5h， 生成 dTMP
  参考文献：
  名称：

  方便合成嘧啶 2'-脱氧核糖核苷单磷酸，在 5 位具有重要的表观遗传标记。

  摘要：

  DNA中胸腺嘧啶的甲基和 5-甲基胞嘧啶 (5 m C) 碱基会受到内源性氧化损伤。此外，5 m C 残基可以通过基因改变或新发现的表观遗传重编程途径进行酶促脱氨基或氧化。已经开发了几种方法来测量修饰的 DNA 核碱基的形成，包括32P-后标记。然而，后标记方法通常受到缺乏真实化学标准的限制。由于修饰碱基上存在额外的官能团，需要复杂的保护和脱保护策略，因此核苷酸氧化产物的单磷酸标准的合成变得复杂。由于对嘧啶氧化产物的兴趣日益浓厚，已经报道了固相寡核苷酸合成所需的相应受保护的 3'-亚磷酰胺，并且有几种是可商购的。我们在此报告了从 3'-亚磷酰胺有效合成 3'-单磷酸酯以及随后使用市售酶将 3'-单磷酸酯酶促转化为相应的 5'-单磷酸酯。

  DOI：

  10.1039/d0ob00884b
• 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 双氧水 作用下， 以 乙腈 为溶剂， 反应 0.25h， 生成 5'-dimethoxytritylthymidine-3'-(biscyanoethyl)monophosphate
  参考文献：
  名称：

  方便合成嘧啶 2'-脱氧核糖核苷单磷酸，在 5 位具有重要的表观遗传标记。

  摘要：

  DNA中胸腺嘧啶的甲基和 5-甲基胞嘧啶 (5 m C) 碱基会受到内源性氧化损伤。此外，5 m C 残基可以通过基因改变或新发现的表观遗传重编程途径进行酶促脱氨基或氧化。已经开发了几种方法来测量修饰的 DNA 核碱基的形成，包括32P-后标记。然而，后标记方法通常受到缺乏真实化学标准的限制。由于修饰碱基上存在额外的官能团，需要复杂的保护和脱保护策略，因此核苷酸氧化产物的单磷酸标准的合成变得复杂。由于对嘧啶氧化产物的兴趣日益浓厚，已经报道了固相寡核苷酸合成所需的相应受保护的 3'-亚磷酰胺，并且有几种是可商购的。我们在此报告了从 3'-亚磷酰胺有效合成 3'-单磷酸酯以及随后使用市售酶将 3'-单磷酸酯酶促转化为相应的 5'-单磷酸酯。

  DOI：

  10.1039/d0ob00884b

文献信息

• Phosphoryl tris-triazole - a new phosphorylating reagent
  作者：Adam Kraszewski、Jacek Stawiński

  DOI：10.1016/s0040-4039(00)78649-7

  日期：1980.1

  Phosphoryl tris-triazole, a new phosphorylating reagent obtained from POCl3 and 1,2,4-triazole, was found to be very useful for the preparation of nucleoside 3′-phosphotriesters bearing various alkyl phosphate protective groups.

  已经发现，从POCl 3和1,2,4-三唑获得的新的磷酸化试剂磷酸三三唑对制备带有各种烷基磷酸酯保护基的核苷3'-磷酸三酯非常有用。
• Modified Immunoenriched ³²P-HPLC Assay for the Detection of <i>O</i>⁴-Ethylthymidine in Human Biomonitoring Studies
  作者：Roger Godschalk、Jagadeesan Nair、Hans-Christian Kliem、Manfred Wiessler、Guy Bouvier、Helmut Bartsch

  DOI：10.1021/tx015582s

  日期：2002.3.1

  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.
• A convenient method for removal of the t-butyl group from nucleoside bis(t-butyl) phosphates under non-acidic conditions
  作者：Mitsuo Sekine、Shin Iimura、Takeshi Nakanishi

  DOI：10.1016/s0040-4039(00)92637-6

  日期：1991.1

  A new method for selective removal of the t-butyl group from 3'-bis(t-butyl) phosphate esters 5'-O-(4,4'-dimethoxytrityl)deoxyribo-nucleosides was developed by use of Me3SiCl and Et3N. Several unexpected properties of the t-butyl group were described.
• Identification of 3,<i>N</i>⁴-Etheno-5-methyl-2′-deoxycytidine in Human DNA: A New Modified Nucleoside Which May Perturb Genome Methylation
  作者：Jagadeesan Nair、Roger W. Godschalk、Urmila Nair、Robert W. Owen、William E. Hull、Helmut Bartsch

  DOI：10.1021/tx200392a

  日期：2012.1.13

  Methylation of cytidine at dCpdG sequences regulates gene expression and is altered in many chronic inflammatory diseases. Inflammation generates lipid peroxidation (LPO) products which can react with deoxycytidine, deoxyadenosine, and deoxyguanosine in DNA to form pro-mutagenic exocyclic etheno-nucleoside residues. Since 5-methyl-2'-deoxycytidine (5mdC) residues exhibit increased nucleophilicity at N3, they should be even better targets for LPO products. We synthesized and characterized 3,N-4-etheno-5-methyl-2'-deoxycytidine-3'-phosphate and showed that LPO products can indeed form the corresponding etheno-5mdC (epsilon 5mdC) lesion in DNA in vitro. Our newly developed P-32-postlabeling method was subsequently used to detect epsilon 5mdC lesions in DNA from human white blood cells, lung, and liver at concentrations 4-10 times higher than that observed for etheno adducts on nonmethylated cytidine. Our new detection method can now be used to explore the hypothesis that this DNA lesion perturbs the DNA methylation status.