N-benzoyl-2'-O-[N2,N6-bis(trifluoroacetyl)lysyl]aminohexyl-5'-O-(4,4'-dimethoxytrityl)adenosine 3'-O-[O-(2-cyanoethyl)-N,N-diisopropylphosphoramidite] | 1242674-93-6

• 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: N-benzoyl-2'-O-[N2,N6-bis(trifluoroacetyl)lysyl]aminohexyl-5'-O-(4,4'-dimethoxytrityl)adenosine 3'-O-[O-(2-cyanoethyl)-N,N-diisopropylphosphoramidite]
• CAS: 1242674-93-6
• 化学式: C₆₃H₇₅F₆N₁₀O₁₁P
• 分子量: 1293.31
• InChiKey: ZUSXRDYMQHGBLN-WJYPCYQQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.62
• 重原子数：
  91.0
• 可旋转键数：
  34.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  251.64
• 氢给体数：
  4.0
• 氢受体数：
  17.0

反应信息

• 作为产物：
  描述：

  2'-O-aminohexyl-5'-O-(4,4'-dimethoxytrityl)adenosine 在 吡啶 、 四氮唑 、 4-二甲氨基吡啶 、 三甲基氯硅烷 、 1-羟基苯并三唑 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 52.0h， 生成 N-benzoyl-2'-O-[N2,N6-bis(trifluoroacetyl)lysyl]aminohexyl-5'-O-(4,4'-dimethoxytrityl)adenosine 3'-O-[O-(2-cyanoethyl)-N,N-diisopropylphosphoramidite]
  参考文献：
  名称：

  2′-O-Lysylaminohexyladenosine modified oligonucleotides

  摘要：

  Development of therapeutically active oligonucleotides for sequence-specific gene knockdown relies on chemical modifications that confer high stability and target affinity and ideally enable cellular uptake. 2'-O-Lysylaminohexyluridine-containing antisense and siRNA oligonucleotides have been shown to be well suited for gene knockdown. They are highly resistant to enzymatic degradation while having good affinity for the targeted RNA strand and efficiently down-regulate their target in cell culture tumor models. The 2'-O-lysylaminohexyl modification was expanded to adenosine nucleosides. The corresponding phosphoramidite building block was prepared in a straightforward procedure comprising six steps starting from adenosine. After 2'-O-alkylation with N-(6-bromohexyl)phthalimide and removal of the N-protecting group, the protected lysine was specifically attached to the alkylamino group. Incorporation of 2'-O-lysylaminohexyladenosine nucleotides in a test sequence confirmed that the cationic chains lead only to minor duplex destabilization and do not disturb the duplex structure. Results further emphasize the advantageous properties of 2'-O-lysylaminohexyl modified oligonucleotides for therapeutic applications.

  DOI：

  10.1007/s00706-010-0318-0