N4,N9-dilinoleoyl-1,12-diamino-4,9-diazadodecane

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: N4,N9-dilinoleoyl-1,12-diamino-4,9-diazadodecane
• 英文别名: N⁴,N⁹-dilinoleoylspermine；(9Z,12Z)-N-(3-aminopropyl)-N-[4-[3-aminopropyl-[(9Z,12Z)-octadeca-9,12-dienoyl]amino]butyl]octadeca-9,12-dienamide
• 化学式: C₄₆H₈₆N₄O₂
• 分子量: 727.214
• InChiKey: MHDOZLYVZXYIHQ-MAZCIEHSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.3
• 重原子数：
  52
• 可旋转键数：
  39
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  92.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  精胺 在 氨 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 108.0h， 生成 N4,N9-dilinoleoyl-1,12-diamino-4,9-diazadodecane
  参考文献：
  名称：

  改变N4，N9-dioctadecanoyl精胺中的不饱和度：非病毒脂多胺载体，可更有效地构建质粒DNA。

  摘要：

  目的：本研究的目的是分析改变合成的N4，N9-二十八碳酰精胺中不饱和度对DNA缩合的影响，然后比较它们在细胞培养中的转染效率。方法：由天然存在的多胺精胺合成N4，N9-di-C18饱和脂肪硬脂胺，硬脂酰基，C9-顺式（油酰基）和C9,12-二顺式（亚油酰基）。使用溴化乙锭荧光猝灭和纳米颗粒表征技术研究了这些新型化合物缩合DNA和形成纳米颗粒的能力。研究了几种原代皮肤细胞（FEK4，FCP4，FCP5，FCP7，和FCP8）和永生化癌细胞系（HtTA）中，并与市售的非脂质体转染制剂Transfectam（二十八碳酰胺基糖基精胺）进行比较，后者也包含两个饱和的C18脂质链。结果：N4，N9-二亚油酰精胺（C18，di-cis-9,12）在环状质粒DNA（pEGFP）缩合反应中非常有效，并且在低电荷比的一系列原代皮肤细胞和癌细胞系中可实现最有效的转染5.5（+/-铵/磷酸盐）。结论：二烯键式脂肪

  DOI：

  10.1007/s11095-005-8717-3

文献信息

• Efficient Silencing of EGFP Reporter Gene with siRNA Delivered by Asymmetrical <i>N</i>⁴,<i>N</i>⁹-Diacyl Spermines
  作者：Abdelkader A. Metwally、Olivier Reelfs、Charareh Pourzand、Ian S. Blagbrough

  DOI：10.1021/mp200429n

  日期：2012.7.2

  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.