2'-O-t-butyldimethylsilyl-N⁶-benzoyl-8-cyclohexylethoxyadenosine | 1402919-77-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2'-O-t-butyldimethylsilyl-N⁶-benzoyl-8-cyclohexylethoxyadenosine
• CAS: 1402919-77-0
• 化学式: C₃₁H₄₅N₅O₆Si
• 分子量: 611.814
• InChiKey: VPBCVAVFAQGXLC-UQCYUJMQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.07
• 重原子数：
  43.0
• 可旋转键数：
  10.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  140.85
• 氢给体数：
  3.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  2'-O-t-butyldimethylsilyl-N⁶-benzoyl-8-cyclohexylethoxyadenosine 在 吡啶 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.08h， 生成 5'-O-(4,4'-dimethoxytrityl)-3'-O-[(2-cyanoethoxy)(N,N-diisopropylamino)phosphino]-2'-O-(t-butyldimethylsilyl)-N6-benzoyl-8-cyclohexylethoxyadenosine
  参考文献：
  名称：

  Promiscuous 8-Alkoxyadenosines in the Guide Strand of an SiRNA: Modulation of Silencing Efficacy and Off-Pathway Protein Binding

  摘要：

  8-Alkoxyadenosines have the potential to exist in anti or syn conformations around the glycosidic bond when paired opposite to U or G in the complementary strands, thereby placing the sterically demanding 8-alkoxy groups in the major or minor groove, respectively, of duplex RNA. These modified bases were used as "base switches" in the guide strands of an siRNA to prevent off-pathway protein binding during delivery via placement of the alkoxy group in the minor groove, while maintaining significant RNAi efficacy by orienting the alkoxy group in the major groove. 8-Alkoxyadenosine phosphoramidites were synthesized and incorporated into the guide strand of caspase 2 siRNA at four different positions: two in the seed region, one at the cleavage Junction, and another nearer to the 3'-end of the guide strand. Thermal stabilities of the corresponding siRNA duplexes showed that U is preferred over G as the base-pairing partner in the complementary strand. When compared to the unmodified positive control siRNAs, singly modified siRNAs knocked down the target mRNA efficiently and with little or no loss of efficacy. Doubly modified siRNAs were found to be less effective and lose their efficacy at low nanomolar concentrations. SiRNAs singly modified at positions 6 and 10 of the guide strand were found to be effective in blocking binding to the RNA-dependent protein kinase PKR, a cytoplasmic dsRNA-binding protein implicated in sequence-independent off-target effects.

  DOI：

  10.1021/ja307102g
• 作为产物：
  描述：

  腺苷 在 吡啶 、 咪唑 、 正丁基锂 、 pyridine hydrofluoride 、 溴 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 39.58h， 生成 2'-O-t-butyldimethylsilyl-N⁶-benzoyl-8-cyclohexylethoxyadenosine
  参考文献：
  名称：

  Promiscuous 8-Alkoxyadenosines in the Guide Strand of an SiRNA: Modulation of Silencing Efficacy and Off-Pathway Protein Binding

  摘要：

  8-Alkoxyadenosines have the potential to exist in anti or syn conformations around the glycosidic bond when paired opposite to U or G in the complementary strands, thereby placing the sterically demanding 8-alkoxy groups in the major or minor groove, respectively, of duplex RNA. These modified bases were used as "base switches" in the guide strands of an siRNA to prevent off-pathway protein binding during delivery via placement of the alkoxy group in the minor groove, while maintaining significant RNAi efficacy by orienting the alkoxy group in the major groove. 8-Alkoxyadenosine phosphoramidites were synthesized and incorporated into the guide strand of caspase 2 siRNA at four different positions: two in the seed region, one at the cleavage Junction, and another nearer to the 3'-end of the guide strand. Thermal stabilities of the corresponding siRNA duplexes showed that U is preferred over G as the base-pairing partner in the complementary strand. When compared to the unmodified positive control siRNAs, singly modified siRNAs knocked down the target mRNA efficiently and with little or no loss of efficacy. Doubly modified siRNAs were found to be less effective and lose their efficacy at low nanomolar concentrations. SiRNAs singly modified at positions 6 and 10 of the guide strand were found to be effective in blocking binding to the RNA-dependent protein kinase PKR, a cytoplasmic dsRNA-binding protein implicated in sequence-independent off-target effects.

  DOI：

  10.1021/ja307102g