N²-phenoxyacetyl-5'-O-dimethoxytrityl-3'-O-[(allyloxy)carbonyl]-2'-deoxyguanosine | 130150-81-1

• 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: N²-phenoxyacetyl-5'-O-dimethoxytrityl-3'-O-[(allyloxy)carbonyl]-2'-deoxyguanosine
• 英文别名: 3'-O-alloxycarbonyl-5'-O-dimethoxytrityl-N2-phenoxyacetyl-2'-deoxyguanosine；5'-O-[Bis(4-methoxyphenyl)(phenyl)methyl]-2'-deoxy-N-(phenoxyacetyl)-3'-O-{[(prop-2-en-1-yl)oxy]carbonyl}guanosine；[(2R,3S,5R)-2-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-5-[6-oxo-2-[(2-phenoxyacetyl)amino]-1H-purin-9-yl]oxolan-3-yl] prop-2-enyl carbonate
• CAS: 130150-81-1
• 化学式: C₄₃H₄₁N₅O₁₀
• 分子量: 787.826
• InChiKey: GWOYYGCWRDPALJ-UQDPWRLZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  58
• 可旋转键数：
  18
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  170
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  N²-phenoxyacetyl-5'-O-dimethoxytrityl-3'-O-[(allyloxy)carbonyl]-2'-deoxyguanosine 在 偶氮二甲酸二异丙酯 、 四丁基氟化铵 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 生成 3'-O-alloxycarbonyl-5'-O-dimethoxytrityl-N2-phenoxyacetyl-O6-(7-hydroxyheptyl)-2'-deoxyguanosine
  参考文献：
  名称：

  包含O 6 -G-烷基-O 6 -G链间交联的寡核苷酸的合成

  摘要：

  已经开发了合成在脱氧鸟苷的两个O 6原子之间包含烷基链间交联的寡核苷酸的方法。该交联被设计为与双功能烷基化剂庚磺胺在双链DNA中形成的病变的稳定结构模拟物。O6-烷基偶联通过核苷与单保护的1,7-庚二醇之间的Mitsunobu反应进行。使用核苷双-亚磷酰胺的固相寡核苷酸合成允许交联双链体的组装。获得足够量的这种交联的双链体用于各种结构和生物学研究。

  DOI：

  10.1016/j.tetlet.2006.10.074
• 作为产物：
  描述：

  苯并三唑-1-基丙-2-烯基碳酸酯 、 5’-O-dimethoxytrityl-N²-phenoxyacetyl-2’-deoxyguanosine 在 4-二甲氨基吡啶 作用下， 以 四氢呋喃 、 吡啶 为溶剂， 反应 24.0h， 以76.2%的产率得到N²-phenoxyacetyl-5'-O-dimethoxytrityl-3'-O-[(allyloxy)carbonyl]-2'-deoxyguanosine
  参考文献：
  名称：

  Synthesis and characterization of an O6-2′-deoxyguanosine-alkyl-O6-2′-deoxyguanosine interstrand cross-link in a 5′-GNC motif and repair by human O6-alkylguanine-DNA alkyltransferase

  摘要：

  已合成了5²-GNC-结构中具有4个和7个亚甲基连接的O6-2²-脱氧鸟苷-烷基-O6-2²-脱氧鸟苷DNA链间交联（ICL），并研究了人类O6-烷基鸟嘌呤-DNA烷基转移酶（hAGT）对其的修复。使用交联的2²-脱氧鸟苷二聚体亚磷酰胺，通过自动DNA固相合成组装了包含11个碱基对的ICL双链，该亚磷酰胺是通过七步合成制备的，其中采用Mitsunobu反应在鸟嘌呤的O6原子引入烷基损伤。与非交联对照相比，引入4个和7个碳的ICL不会改变双链的稳定性（基于UV热变性实验）。这些ICL双链的圆二色光谱表现出与对照类似的B型双链特征，表明这些损伤不会引起整体结构变化。研究了hAGT的修复效率，结果表明，hAGT可以修复两种ICL双链，其中庚基ICL的修复效率比丁基交联更高。这些结果在各种hAGT突变体中具有可重复性，包括一种含有新型V148L突变的突变体。与未修饰的双链相比，ICL双链与C

  DOI：

  10.1039/c0ob00093k

文献信息

• Synthesis and characterization of an O6-2′-deoxyguanosine-alkyl-O6-2′-deoxyguanosine interstrand cross-link in a 5′-GNC motif and repair by human O6-alkylguanine-DNA alkyltransferase
  作者：Francis P. McManus、Qingming Fang、Jason D. M. Booth、Anne M. Noronha、Anthony E. Pegg、Christopher J. Wilds

  DOI：10.1039/c0ob00093k

  日期：——

  O6-2′-Deoxyguanosine-alkyl-O6-2′-deoxyguanosine interstrand DNA cross-links (ICLs) with a four and seven methylene linkage in a 5′-GNC- motif have been synthesized and their repair by human O6-alkylguanine-DNA alkyltransferase (hAGT) investigated. Duplexes containing 11 base-pairs with the ICLs in the center were assembled by automated DNA solid-phase synthesis using a cross-linked 2′-deoxyguanosine dimer phosphoramidite, prepared via a seven step synthesis which employed the Mitsunobu reaction to introduce the alkyl lesion at the O6 atom of guanine. Introduction of the four and seven carbon ICLs resulted in no change in duplex stability based on UV thermal denaturation experiments compared to a non-cross-linked control. Circular dichroism spectra of these ICL duplexes exhibited features of a B-form duplex, similar to the control, suggesting that these lesions induce little overall change in structure. The efficiency of repair by hAGT was examined and it was shown that hAGT repairs both ICL containing duplexes, with the heptyl ICL repaired more efficiently relative to the butyl cross-link. These results were reproducible with various hAGT mutants including one that contains a novel V148L mutation. The ICL duplexes displayed similar binding affinities to a C145S hAGT mutant compared to the unmodified duplex with the seven carbon containing ICLs displaying slightly higher binding. Experiments with CHO cells to investigate the sensitivity of these cells to busulfan and hepsulfam demonstrate that hAGT reduces the cytotoxicity of hepsulfam suggesting that the O6-2′-deoxyguanosine-alkyl-O6-2′-deoxyguanosine interstrand DNA cross-link may account for at least part of the cytotoxicity of this agent.

  已合成了5²-GNC-结构中具有4个和7个亚甲基连接的O6-2²-脱氧鸟苷-烷基-O6-2²-脱氧鸟苷DNA链间交联（ICL），并研究了人类O6-烷基鸟嘌呤-DNA烷基转移酶（hAGT）对其的修复。使用交联的2²-脱氧鸟苷二聚体亚磷酰胺，通过自动DNA固相合成组装了包含11个碱基对的ICL双链，该亚磷酰胺是通过七步合成制备的，其中采用Mitsunobu反应在鸟嘌呤的O6原子引入烷基损伤。与非交联对照相比，引入4个和7个碳的ICL不会改变双链的稳定性（基于UV热变性实验）。这些ICL双链的圆二色光谱表现出与对照类似的B型双链特征，表明这些损伤不会引起整体结构变化。研究了hAGT的修复效率，结果表明，hAGT可以修复两种ICL双链，其中庚基ICL的修复效率比丁基交联更高。这些结果在各种hAGT突变体中具有可重复性，包括一种含有新型V148L突变的突变体。与未修饰的双链相比，ICL双链与C
• Synthesis of oligonucleotides containing an O6-G-alkyl-O6-G interstrand cross-link
  作者：Christopher J. Wilds、Jason D. Booth、Anne M. Noronha

  DOI：10.1016/j.tetlet.2006.10.074

  日期：2006.12

  A methodology to synthesize oligonucleotides containing an alkyl interstrand cross-link between the two O6 atoms of deoxyguanosine has been developed. This cross-link is designed to serve as a stable structural mimic of the lesion formed in duplex DNA with the bifunctional alkylating agent hepsulfam. The O6-alkyl coupling is performed via a Mitsunobu reaction between a nucleoside and mono-protected

  已经开发了合成在脱氧鸟苷的两个O 6原子之间包含烷基链间交联的寡核苷酸的方法。该交联被设计为与双功能烷基化剂庚磺胺在双链DNA中形成的病变的稳定结构模拟物。O6-烷基偶联通过核苷与单保护的1,7-庚二醇之间的Mitsunobu反应进行。使用核苷双-亚磷酰胺的固相寡核苷酸合成允许交联双链体的组装。获得足够量的这种交联的双链体用于各种结构和生物学研究。