d[TpApT] | 59189-02-5

• 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: d[TpApT]
• 英文别名: thymidylyl-(3'->5')-2'-deoxy-adenylyl-(3'->5')-thymidine；d-(T-pA-pT)；dThd-P-dAdo-P-dThd；[(2R,3S,5R)-5-(6-aminopurin-9-yl)-3-[hydroxy-[[(2R,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]phosphoryl]oxyoxolan-2-yl]methyl [(2R,3S,5R)-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl] hydrogen phosphate
• CAS: 59189-02-5
• 化学式: C₃₀H₃₉N₉O₁₇P₂
• 分子量: 859.637
• InChiKey: SJHVRRLLSWLQQT-JGGRBJFDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4.7
• 重原子数：
  58
• 可旋转键数：
  14
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  348
• 氢给体数：
  7
• 氢受体数：
  21

反应信息

• 作为反应物：
  描述：

  d[TpApT] 、 聚合甲醛 、 N-Boc-L-组氨酸 生成
  参考文献：
  名称：

  氨基酸和脱氧核苷及其低聚物之间甲醛诱导交联的结构表征

  摘要：

  接触甲醛会导致 DNA-蛋白质交联 (DPC) 的形成，这是主要的遗传毒性作用。尽管 DPC 在生物学上很重要，据报道有八种氨基酸与甲醛形成稳定的加合物，但这些交联的结构尚未阐明。我们已经表征了甲醛诱导的 Lys、Cys、His 和 Trp 与 dG、dA 和 dC 的交联。dT 没有形成交联，Arg、Gln、Tyr 或 Asn 也没有形成。甲醛与 Lys 和 dG 的反应产生了最高的交联产物，其次是与 Cys 和 dG 的反应。其他偶联反应的产率降低了 10 倍或更多。核磁共振和质谱的详细结构检查确定氨基酸和单个核苷之间的交联涉及甲醛衍生的亚甲基桥。Lys 产生了两个额外的产品与 dG，其中的链接结构是 1，N(2)-融合的三嗪环。Lys 交联产物在环境温度下不稳定。反应性 N(α)-Boc 保护的氨基酸与三核苷酸 d(T(1)B(2)T(3)) 之间的反应，其中 B(2) 是目标碱基 G、A

  DOI：

  10.1021/ja908282f
• 作为产物：
  描述：

  Ura-Ribf2Me-P-Ade-Ribf2Me-P-dThd 在 氨 、 水 作用下， 反应 12.0h， 生成 d[TpApT]
  参考文献：
  名称：

  O-Selective Condensation Using P−N Bond Cleavage in RNA Synthesis without Base Protection

  摘要：

  In RNA synthesis without base protection, a new method for O-selective condensation with more than 99% selectivity was developed by 6-nitro-HOBt-mediated cleavage of undesired P(III)-N bonds on nucleobase moieties. Moreover, we for the first time succeeded in synthesizing oligoRNAs without base protection.

  DOI：

  10.1021/ol800911b

文献信息

• O-Selectivity and Utility of Phosphorylation Mediated by Phosphite Triester Intermediates in the N-Unprotected Phosphoramidite Method
  作者：Akihiro Ohkubo、Yusuke Ezawa、Kohji Seio、Mitsuo Sekine

  DOI：10.1021/ja048125h

  日期：2004.9.1

  molecular orbital interactions between the reactive intermediates and the nucleophiles such as the amino or hydroxyl groups of nucleosides. Furthermore, longer oligonucleotides were synthesized not only by a manual operation but also by a DNA synthesizer. The utility of our new method was demonstrated by the successful synthesis of a base-labile modified oligodeoxyribonucleotide having 4-N-acetyldeoxycytidine

  以前，由于 dA 和 dC 的氨基对三价磷 (III) 型亚磷酸化试剂具有高反应性，因此无法在 N-未保护的亚磷酰胺方法中进行聚合物载体上的 O 选择性磷酸化。在本文中，我们开发了一种名为“活化亚磷酸酯方法”的新偶联策略，其中亚磷酸三酯中间体 1 介导了亚磷酸化。将 1-羟基苯并三唑作为促进剂应用于固相合成导致了优异的 O-选择性超过 99.7%。这种 O 选择性可以通过反应中间体和亲核试剂（如核苷的氨基或羟基）之间的前沿分子轨道相互作用来解释。此外，更长的寡核苷酸不仅可以通过手动操作合成，也可以通过 DNA 合成仪合成。通过成功合成具有 4-N-乙酰脱氧胞苷残基的碱不稳定修饰寡脱氧核糖核苷酸，证明了我们新方法的实用性。最后，通过使用 6-三氟甲基-1-羟基苯并三唑和苯并咪唑鎓三氟甲磺酸盐的组合试剂，可以以良好的产率合成含有 dA 或 dC 的 DNA 20 聚体。
• A new strategy for the synthesis of oligodeoxynucleotides directed towards perfect O-selective internucleotidic bond formation without base protection
  作者：Akihiro Ohkubo、Kohji Seio、Mitsuo Sekine

  DOI：10.1016/j.tetlet.2003.10.156

  日期：2004.1

  Deoxyadenosine and deoxycytidine have nucleophilic amino groups so that the undesired N-phosphitylation of these amino groups occurred in the previous phosphoramidite methods without base protection. We report that the N-phosphitylation could be considerably suppressed in our new HOBt-mediated coupling strategy via phosphite intermediates as reactive species. Thus, 99.7-99.9% O-selective internucleotidic bond formation was achieved. (C) 2003 Published by Elsevier Ltd.
• Formation of Modified Cytosine Residues in the Presence of Depurinated DNA
  作者：Claus Rentel、Xiaojing Wang、Michael Batt、Christine Kurata、Jay Oliver、Hans Gaus、Achim H. Krotz、James V. McArdle、Daniel C. Capaldi

  DOI：10.1021/jo050767f

  日期：2005.9.1

  Depurination is an important degradation pathway for antisense phosphorothioate oligonucleotides under conditions of thermal stress. We present evidence showing that depurinated oligonucleotides react with cytosine-containing sequences giving products containing a 6-(2-deoxy-beta-D-erythropentofuranosyl)-3-(2-oxopropyl)imidazo[1,2-c]pyrimidin-5(6H)-one residue. Further, we demonstrate that the same product is formed upon treatment of 2'-deoxycytidine with 4-oxo-2-pentenal, the latter being an expected byproduct of serial elimination reactions at apurinic sites. In addition to being important for synthetic oligonucleotides, apurinic site formation in cellular DNA is a common occurrence. Because repair of these sites can result in the production of 4-oxo-2-pentenal, it is interesting to speculate whether 6-(2-deoxy-beta-D-erythro-pentofuranosyl)-3-(2-oxopropyl)imidazo[1,2-c]pyrimidin-5(6H)-one residues can form in vivo.
• Structural Characterization of Formaldehyde-Induced Cross-Links Between Amino Acids and Deoxynucleosides and Their Oligomers
  作者：Kun Lu、Wenjie Ye、Li Zhou、Leonard B. Collins、Xian Chen、Avram Gold、Louise M Ball、James A. Swenberg

  DOI：10.1021/ja908282f

  日期：2010.3.17

  the formation of DNA-protein cross-links (DPCs) as a primary genotoxic effect. Although DPCs are biologically important and eight amino acids have been reported to form stable adducts with formaldehyde, the structures of these cross-links have not yet been elucidated. We have characterized formaldehyde-induced cross-links of Lys, Cys, His, and Trp with dG, dA, and dC. dT formed no cross-links, nor

  接触甲醛会导致 DNA-蛋白质交联 (DPC) 的形成，这是主要的遗传毒性作用。尽管 DPC 在生物学上很重要，据报道有八种氨基酸与甲醛形成稳定的加合物，但这些交联的结构尚未阐明。我们已经表征了甲醛诱导的 Lys、Cys、His 和 Trp 与 dG、dA 和 dC 的交联。dT 没有形成交联，Arg、Gln、Tyr 或 Asn 也没有形成。甲醛与 Lys 和 dG 的反应产生了最高的交联产物，其次是与 Cys 和 dG 的反应。其他偶联反应的产率降低了 10 倍或更多。核磁共振和质谱的详细结构检查确定氨基酸和单个核苷之间的交联涉及甲醛衍生的亚甲基桥。Lys 产生了两个额外的产品与 dG，其中的链接结构是 1，N(2)-融合的三嗪环。Lys 交联产物在环境温度下不稳定。反应性 N(α)-Boc 保护的氨基酸与三核苷酸 d(T(1)B(2)T(3)) 之间的反应，其中 B(2) 是目标碱基 G、A
• <i>O</i>-Selective Condensation Using P−N Bond Cleavage in RNA Synthesis without Base Protection
  作者：Akihiro Ohkubo、Yasukazu Kuwayama、Tomomi Kudo、Hirosuke Tsunoda、Kohji Seio、Mitsuo Sekine

  DOI：10.1021/ol800911b

  日期：2008.7.3

  In RNA synthesis without base protection, a new method for O-selective condensation with more than 99% selectivity was developed by 6-nitro-HOBt-mediated cleavage of undesired P(III)-N bonds on nucleobase moieties. Moreover, we for the first time succeeded in synthesizing oligoRNAs without base protection.