5’-O-dimethoxytrityl-N²-phenoxyacetyl-2’-deoxyguanosine | 110522-81-1

• 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: 5’-O-dimethoxytrityl-N²-phenoxyacetyl-2’-deoxyguanosine
• 英文别名: N²-phenoxyacetyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxyguanosine；5'-O-(4,4'-dimethoxytrityl)-N²-phenoxyacetyl-2'-deoxyguanosine；5'-O-dimethoxytrityl-N2-phenoxyacetyl-2'-deoxyguanosine；N2-phenoxyacetyl-5'-O-(4,4'-dimethoxytrityl)-2'-deoxyguanosine；N-[9-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxyoxolan-2-yl]-6-oxo-1H-purin-2-yl]-2-phenoxyacetamide
• CAS: 110522-81-1
• 化学式: C₃₉H₃₇N₅O₈
• 分子量: 703.751
• InChiKey: RGMDCYXYFWPCBM-VOTWKOMSSA-N

物化性质

• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  52
• 可旋转键数：
  13
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  155
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  5’-O-dimethoxytrityl-N²-phenoxyacetyl-2’-deoxyguanosine 在 lutidine 、 乙二胺 作用下， 以 四氢呋喃 、 ammonium hydroxide 、 乙醇 、 乙腈 为溶剂， 反应 4.5h， 生成 Acetic acid (2R,3S,5R)-5-(2-acetylamino-6-oxo-1,6-dihydro-purin-9-yl)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-tetrahydro-furan-3-yl ester
  参考文献：
  名称：

  Synthesis of Oligodeoxyribonucleoside Methylphosphonates Containing 2-Aminopurine

  摘要：

  Oligodeoxyribonucleoside methylphosphonates containing multiple 2-aminopurine bases were synthesized by solid-phase phosphonamidite chemistry for investigating their triple helix formation with natural DNA or other duplex targets and for cellular uptake studies of the methylphosphonate oligomers. The base-labile phenoxyacetyl group was used as the N-2-amino protecting group for 2-aminopurine, allowing the final deprotection of the oligomers to be performed under the standard ethylenediamine condition.

  DOI：

  10.1080/07328319608002463
• 作为产物：
  描述：

  2'-脱氧鸟苷 在 吡啶 、 水 、 三乙胺 作用下， 生成 5’-O-dimethoxytrityl-N²-phenoxyacetyl-2’-deoxyguanosine
  参考文献：
  名称：

  轻松去除可用于寡核苷酸合成的新碱基保护基

  摘要：

  提出了新的碱保护基团来代替苯甲酰基和异丁酰基。对于腺嘌呤和鸟嘌呤，它们是苯氧基乙酰基；对于胞嘧啶，它们是异丁酰基。它们在较低的温度下在较短的时间内在氨水中裂解。这些易于除去的基团可用于合成含有易碎碱基的修饰寡核苷酸。

  DOI：

  10.1016/s0040-4039(00)95646-6

文献信息

• PHOSPHORAMIDITE BUILDING BLOCKS FOR SUGAR-CONJUGATED OLIGONUCLEOTIDES
  申请人：AM CHEMICALS LLC

  公开号：US20160083414A1

  公开（公告）日：2016-03-24

  Novel nucleoside phosphoramidite building blocks for preparation of synthetic oligonucleotides containing at least one phosphotriester linkage conjugated to a monosaccharide and synthetic processes for making the same are disclosed. Furthermore, oligomeric compounds are prepared using said building blocks, preferably followed by removal of protecting groups to provide monosaccharide-conjugated oligonucleotides.

  揭示了用于制备含至少一种磷酸三酯键连接的寡核苷酸的合成寡核苷酸的新型核苷酸磷酰胺酯构建模块，其与单糖偶联，并公开了制备这些构建模块的合成过程。此外，使用这些构建模块制备寡聚合物化合物，最好是在去除保护基之后，以提供单糖偶联的寡核苷酸。
• Synthesis, Characterization, and Repair of a Flexible<i>O</i>⁶-2′-Deoxyguanosine-alkylene-<i>O</i>⁶-2′-deoxyguanosine Intrastrand Cross-Link
  作者：Derek K. O'Flaherty、Christopher J. Wilds

  DOI：10.1002/chem.201501103

  日期：2015.7.13

  Oligonucleotides tethered by an alkylene linkage between the O6‐atoms of two consecutive 2′‐deoxyguanosines, which lack a phosphodiester linkage between these residues, have been synthesized as a model system of intrastrand cross‐linked (IaCL) DNA. UV thermal denaturation studies of duplexes formed between these butylene‐ and heptylene‐linked oligonucleotides with their complementary DNA sequences revealed about

  作为两个链内交联（IaCL）DNA的模型系统，已经合成了通过两个连续的2'-脱氧鸟苷的O 6原子之间的亚烷基键束缚的寡核苷酸，这些残基之间没有磷酸二酯键。这些丁烯和庚烯连接的寡核苷酸及其互补的DNA序列之间形成的双链体的UV热变性研究表明，相对于未修饰的双链体，其稳定性降低了约20°C。模型IaCL双链体的圆二色性光谱显示了B型DNA的特征，表明病变引起的总体扰动最小。研究了包含IaCL模型的双链体作为O 6的底物来自人和大肠杆菌（Ada-C和OGT）的-烷基鸟嘌呤DNA烷基转移酶（AGT）蛋白。发现人类AGT可以修复两种IaCL双链体，对庚烯和丁烯类似物的修复效率更高，这进一步增加了我们对该蛋白可以修复的底物的了解。
• O ⁶ ‐Alkylguanine DNA Alkyltransferase Mediated Disassembly of a DNA Tetrahedron
  作者：William Copp、Christopher J. Wilds

  DOI：10.1002/chem.202002565

  日期：2020.11.20

  Tetrahedron DNA structures were formed by the assembly of three‐way junction (TWJ) oligonucleotides containing O6‐2′‐deoxyguanosine‐alkylene‐O6‐2′‐deoxyguanosine (butylene and heptylene linked) intrastrand cross‐links (IaCLs) lacking a phosphodiester group between the 2′‐deoxyribose residues. The DNA tetrahedra containing TWJs were shown to undergo an unhooking reaction by the human DNA repair protein

  四面体DNA结构经装配三通结（形成TWJ）含有寡核苷酸Ô 6 -2'-脱氧鸟苷-亚烷基- ö 6 -2'-脱氧鸟苷链内（丁烯和亚庚基联）的交联（IaCLs）缺乏2'-脱氧核糖残基之间的磷酸二酯基。含有TWJ的DNA四面体已被人类DNA修复蛋白O 6进行脱钩反应‐烷基鸟嘌呤DNA烷基转移酶（hAGT）导致结构分解。观察到hAGT对DNA四面体的解钩反应是中等至几乎完全完成的，这取决于蛋白质的当量。DNA四面体结构已被研究为一种药物传递平台，可以响应光，化学试剂或释放链的杂交等触发条件而释放其有效负载。DNA修复蛋白对DNA四面体结构的分解有助于采用DNA纳米结构的药物释放方法的集结。
• 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
• SCHULHOF, J. C.;MOLKO, D.;TEOULE, R., BIOPHOSPHAT. AND ANALOGUES: SYNTH., STUCT., METAB. AND ACTIV. PROC. 2ND I+
  作者：SCHULHOF, J. C.、MOLKO, D.、TEOULE, R.

  DOI：——

  日期：——