d[TpGpT] | 54230-74-9

• 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[TpGpT]
• 英文别名: d(TGT)；TdGT；dThd-P-dGuo-P-dThd；[(2R,3S,5R)-5-(2-amino-6-oxo-1H-purin-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: 54230-74-9
• 化学式: C₃₀H₃₉N₉O₁₈P₂
• 分子量: 875.637
• InChiKey: WBGRGIDIQDIONM-FGQYFZLASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.5
• 重原子数：
  59
• 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：
  364
• 氢给体数：
  8
• 氢受体数：
  20

反应信息

• 作为反应物：
  描述：

  d[TpGpT] 在 nuclease P₁ 、 calcium chloride 、 维生素 B2 作用下， 以 水 为溶剂， 反应 96.5h， 生成
  参考文献：
  名称：

  Characterization of Lysine−Guanine Cross-Links upon One-Electron Oxidation of a Guanine-Containing Oligonucleotide in the Presence of a Trilysine Peptide

  摘要：

  Formation of DNA-protein cross-links involving the initial formation of a guanine radical cation was investigated. For this purpose, riboflavin-mediated photosensitization of a TGT oligonucleotide in aerated aqueous solution in the presence of the KKK tripeptide was performed. We have shown that the nucleophilic addition of the c-amino group of the central lysine residue of KKK to the C8 atom of either the guanine radical cation or its deprotonated form gives rise to the efficient formation of a N epsilon-(guanin-8-yl)-lysine cross-link. Interestingly, the time course of formation of the above-mentioned cross-link was found to be not linear with the time of irradiation, and its formation rapidly reached a plateau. This is explained by secondary decomposition of the initially generated cross-link which could be further oxidized more efficiently than starting TGT oligonucleotide. One-electron oxidation of the initially generated cross-link was found to produce mainly two diastereomeric cross-links exhibiting a spiroimino-trilysine-dihydantoin structure as inferred from enzymatic digestion, CD, UV, NMR and mass spectrometry measurements. In addition, other minor crosslinks, for which formation was favored at acidic pH, were assigned as lysine-guanine adducts in which the modified guanine base exhibits a guanidino-trilysine-iminohydantoin structure. A proposed mechanism for the formation of the different detected oligonucleotide-peptide cross-links is given. The high yield of formation of the detected cross-links strongly suggests that a DNA-protein cross-link involving a lysine residue linked to the C8 position of guanine could be generated in cellular systems if a lysine is located in the close vicinity of a guanine radical cation.

  DOI：

  10.1021/ja057656i
• 作为产物：
  描述：

  5’-(4,4’-二甲氧基三苯基)-3’-脱氧胸苷 2’-(2-氰乙基-N,N-二异丙基)亚磷酰胺 、 5'-O-dimethoxytrityl-N2-isobutyryl-2'-deoxyguanosine-3'-O-(2-cyanoethyl)-N,N-diisopropylphosphoramidite 生成 d[TpGpT]
  参考文献：
  名称：

  Formation of Modified Cytosine Residues in the Presence of Depurinated DNA

  摘要：

  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.

  DOI：

  10.1021/jo050767f

文献信息

• 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
• 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。
• Copper carbenes alkylate guanine chemoselectively through a substrate directed reaction
  作者：Stefanie N. Geigle、Laura A. Wyss、Shana J. Sturla、Dennis G. Gillingham

  DOI：10.1039/c6sc03502g

  日期：——

  Cu(I) carbenes derived from α-diazocarbonyl compounds lead to selective alkylation of the O6 position in guanine (O6-G) in mono- and oligonucleotides. Only purine-type lactam oxygens are targeted – other types of amides or lactams are poorly reactive under conditions that give smooth alkylation of guanine. Mechanistic studies point to N7G as a directing group that controls selectivity. Given the importance

  衍生自 α-重氮羰基化合物的 Cu() 卡宾可导致单核苷酸和寡核苷酸中鸟嘌呤 (O 6 -G) 中 O 6位的选择性烷基化。只有嘌呤型内酰胺氧是目标——其他类型的酰胺或内酰胺在鸟嘌呤顺利烷基化的条件下反应性较差。机理研究表明 N7G 作为控制选择性的指导基团。鉴于O 6 -G加合物在生物学和生物技术中的重要性，我们预计Cu()催化的O 6 -G烷基化将成为广泛使用的合成工具。虽然过渡金属增加氧化还原损伤的倾向已得到广泛认可，但我们的结果表明过渡金属也可能增加核酸对烷基化损伤的脆弱性。
• 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.