1,12-diphthalimido-N4-oleoyl-4,9-diazadodecane | 1352529-28-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 1,12-diphthalimido-N4-oleoyl-4,9-diazadodecane
• CAS: 1352529-28-2
• 化学式: C₄₄H₆₂N₄O₅
• 分子量: 727.0
• InChiKey: PQXVZDMWJVTTTM-KTKRTIGZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.59
• 重原子数：
  53.0
• 可旋转键数：
  28.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  107.1
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  1,12-diphthalimido-N4-oleoyl-4,9-diazadodecane 在 4-二甲氨基吡啶 、 一水合肼 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 N4-arachidonoyl-N9-oleoyl-1,12-diamino-4,9-diazadodecane
  参考文献：
  名称：

  Efficient Silencing of EGFP Reporter Gene with siRNA Delivered by Asymmetrical N⁴,N⁹-Diacyl Spermines

  摘要：

  It is important to obtain structure-activity relationship (SAR) data across cationic lipids for the self-assembly and nonviral intracellular delivery of siRNA. The aims of this work are to carry out a SAR study on the efficiency of asymmetrical N-4,N-9-diacyl spermines in siRNA delivery and EGFP reporter gene silencing, with comparisons to selected mixtures composed of symmetrical N-4,N-9-diacyl spermines. Another important aim of these studies is to quantify the changes in cell viability, assayed with alamarBlue, as a function of lipid structure. Therefore, we have designed, synthesized, purified, and assayed novel cationic lipids that are asymmetrical lipopolyamines based on spermine. Flow cytometry and fluorescence microscopy in an EGFP stably transfected HeLa cell line, measuring both delivery of fluorescently tagged siRNAs and silencing the EGFP signal, allowed quantitation of the differences between asymmetrical cationic lipids, mixtures of their symmetrical counterparts, and comparison with commercial nonviral delivery agents. Intracellular delivery of siRNA and gene silencing by siRNA differ with different hydrophobic domains. In these asymmetrical N-4,N-9-diacyl spermines, lipids that enhance siRNA uptake do not necessarily enhance siRNA-induced inhibition of gene expression: C18 and longer saturated chains promote uptake, while more unsaturated C18 chains promote gene silencing. These properties are efficiently demonstrated in a new nontoxic cationic lipid siRNA vector, N-4-linoleoyl-N-9-oleoyl-1,12-diamino-4,9-diazadodecane (LinOS), which is also shown to be comparable with or superior to TransIT-TKO and Lipofectamine 2000.

  DOI：

  10.1021/mp200429n
• 作为产物：
  描述：

  精胺 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 23.0h， 生成 1,12-diphthalimido-N4-oleoyl-4,9-diazadodecane
  参考文献：
  名称：

  Efficient Silencing of EGFP Reporter Gene with siRNA Delivered by Asymmetrical N⁴,N⁹-Diacyl Spermines

  摘要：

  It is important to obtain structure-activity relationship (SAR) data across cationic lipids for the self-assembly and nonviral intracellular delivery of siRNA. The aims of this work are to carry out a SAR study on the efficiency of asymmetrical N-4,N-9-diacyl spermines in siRNA delivery and EGFP reporter gene silencing, with comparisons to selected mixtures composed of symmetrical N-4,N-9-diacyl spermines. Another important aim of these studies is to quantify the changes in cell viability, assayed with alamarBlue, as a function of lipid structure. Therefore, we have designed, synthesized, purified, and assayed novel cationic lipids that are asymmetrical lipopolyamines based on spermine. Flow cytometry and fluorescence microscopy in an EGFP stably transfected HeLa cell line, measuring both delivery of fluorescently tagged siRNAs and silencing the EGFP signal, allowed quantitation of the differences between asymmetrical cationic lipids, mixtures of their symmetrical counterparts, and comparison with commercial nonviral delivery agents. Intracellular delivery of siRNA and gene silencing by siRNA differ with different hydrophobic domains. In these asymmetrical N-4,N-9-diacyl spermines, lipids that enhance siRNA uptake do not necessarily enhance siRNA-induced inhibition of gene expression: C18 and longer saturated chains promote uptake, while more unsaturated C18 chains promote gene silencing. These properties are efficiently demonstrated in a new nontoxic cationic lipid siRNA vector, N-4-linoleoyl-N-9-oleoyl-1,12-diamino-4,9-diazadodecane (LinOS), which is also shown to be comparable with or superior to TransIT-TKO and Lipofectamine 2000.

  DOI：

  10.1021/mp200429n