5'-dimethoxytrityl-2-isobutyramido-N6-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)-2'-deoxyadenosine-3'-(2-cyanoethyl-N,Ndiisopropyl) phosphoramidite | 342630-72-2

• 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'-dimethoxytrityl-2-isobutyramido-N6-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)-2'-deoxyadenosine-3'-(2-cyanoethyl-N,Ndiisopropyl) phosphoramidite
• CAS: 342630-72-2
• 化学式: C₅₃H₇₃N₉O₈P
• 分子量: 995.192
• InChiKey: FQDBPUBOUVZFHG-WWCGDYRGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  71
• 可旋转键数：
  21
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  171
• 氢给体数：
  2
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  2,2,6,6-四甲基-4-哌啶酮肟 在 吡啶 、 四氮唑 、 4-二甲氨基吡啶 、 ammonium hydroxide 、 sodium tungstate 、 lithium aluminium tetrahydride 、 双氧水 、 ethylene diamine tetraacetic acid tetrasodium salt 、 sodium carbonate 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 74.0h， 生成 5'-dimethoxytrityl-2-isobutyramido-N6-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)-2'-deoxyadenosine-3'-(2-cyanoethyl-N,Ndiisopropyl) phosphoramidite
  参考文献：
  名称：

  Electron Paramagnetic Resonance (EPR) Study of Spin-Labeled Camptothecin Derivatives: A Different Look of the Ternary Complex

  摘要：

  Camptothecin (CPT) derivatives are clinically effective poisons of DNA topoisomerase I (Top 1) able to form a ternary complex with the Top1 DNA complex. The aim of this investigation was to examine the dynamic aspects of the ternary complex formation by means of site-directed spin labeling electron paramagnetic resonance (SDSL-EPR). Two semisynthetic CPT derivatives bearing the paramagnetic moiety were synthesized, and their biological activity was tested. A 22-mer DNA oligonucleotide sequence with high affinity cleavage site for Top1 was also synthesized. EPR experiments were carried out on modified CPT in the presence of DNA, of Top1, or of both. In the last case, a slow motion component in the EPR signal appeared, indicating the formation of the ternary complex. Deconvolution of the EPR spectrum allowed to obtain the relative drug amounts in the complex. It was also possible to demonstrate that the residence time of CPT "trapped" in the ternary complex is longer than hundreds of microseconds.

  DOI：

  10.1021/jm101232t

文献信息

• Preparation of Spin-Labeled-2-Amino-dA, dA, dC and 5-Methyl-dC Phosphoramidites for the Automatic Synthesis of EPR Active Oligonucleotides
  作者：Cesare Giordano、Federica Fratini、Donato Attanasio、Luciano Cellai

  DOI：10.1055/s-2001-12355

  日期：——

  2,2,6,6-Tetramethyl-1-piperidinyloxy free radical (TEMPO) labeled phosphoramidites of 2-amino-dA, dA, dC and 5-methyl-dC were synthesized and used for the automatic synthesis of mono-labeled oligodeoxynucleotides (ODNs), which proved active to EPR. It is now possible to insert a paramagnetic probe into nucleic acids in a site- and type-specific manner. The combination of this synthetic approach with EPR spectroscopy can be exploited for performing studies on dynamics and local structural modifications in nucleic acids.

  合成了2,2,6,6-四甲基-1-哌啶氧自由基（TEMPO）标记的2-氨基-dA、dA、dC和5-甲基-dC的磷酰胺类化合物，并用于单标记寡脱氧核苷酸（ODNs）的自动合成，这些化合物对电子顺磁共振（EPR）表现出活性。现在可以以特定的位置和类型将顺磁探针插入核酸中。这种合成方法与EPR光谱的结合可以用于研究核酸中的动态变化和局部结构修饰。
• Electron Paramagnetic Resonance (EPR) Study of Spin-Labeled Camptothecin Derivatives: A Different Look of the Ternary Complex
  作者：Antonio Ricci、Jessica Marinello、Marco Bortolus、Albert Sánchez、Anna Grandas、Enrique Pedroso、Yves Pommier、Giovanni Capranico、Anna Lisa Maniero、Giuseppe Zagotto

  DOI：10.1021/jm101232t

  日期：2011.2.24

  Camptothecin (CPT) derivatives are clinically effective poisons of DNA topoisomerase I (Top 1) able to form a ternary complex with the Top1 DNA complex. The aim of this investigation was to examine the dynamic aspects of the ternary complex formation by means of site-directed spin labeling electron paramagnetic resonance (SDSL-EPR). Two semisynthetic CPT derivatives bearing the paramagnetic moiety were synthesized, and their biological activity was tested. A 22-mer DNA oligonucleotide sequence with high affinity cleavage site for Top1 was also synthesized. EPR experiments were carried out on modified CPT in the presence of DNA, of Top1, or of both. In the last case, a slow motion component in the EPR signal appeared, indicating the formation of the ternary complex. Deconvolution of the EPR spectrum allowed to obtain the relative drug amounts in the complex. It was also possible to demonstrate that the residence time of CPT "trapped" in the ternary complex is longer than hundreds of microseconds.