| 1357913-77-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• CAS: 1357913-77-9
• 化学式: C₆₉H₁₁₆N₈O₆
• 分子量: 1153.73
• InChiKey: FKWNVGWEYHDKBZ-MPXDMKPJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  15.27
• 重原子数：
  83.0
• 可旋转键数：
  28.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  186.86
• 氢给体数：
  4.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  、 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 24.0h， 以71%的产率得到
  参考文献：
  名称：

  Synergistic effects in gene delivery—a structure–activity approach to the optimisation of hybrid dendritic–lipidic transfection agents

  摘要：

  基于胆固醇单元与精胺功能化树枝状分子相结合的新型基因传递剂具有增强的转染能力——我们报告了在混合（杂合）系统中显著的协同效应，该系统结合了阳离子聚合物和脂质这两种主要合成载体类别的各个方面。

  DOI：

  10.1039/b811852c
• 作为产物：
  描述：

  dimethyl 3,3'-((3-azidopropyl)azanediyl)dipropionate 在 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Degradable Self-Assembling Dendrons for Gene Delivery: Experimental and Theoretical Insights into the Barriers to Cellular Uptake

  摘要：

  This paper uses a combined experimental and theoretical approach to gain unique insight into gene delivery. We report the synthesis and investigation of a new family of second-generation dendrons with four triamine surface ligands capable of binding to DNA, degradable aliphatic-ester dendritic scaffolds, and hydrophobic units at their focal points. Dendron self-assembly significantly enhances DNA binding as monitored by a range of experimental methods and confirmed by multiscale modeling. Cellular uptake studies indicate that some of these dendrons are highly effective at transporting DNA into cells (ca. 10 times better than poly(ethyleneimine), PEI). However, levels of transgene expression are relatively low (ca. 10% of PEI). This indicates that these dendrons cannot navigate all of the intracellular barriers to gene delivery. The addition of chloroquine indicates that endosomal escape is not the limiting factor in this case, and it is shown, both experimentally and theoretically, that gene delivery can be correlated with the ability of the dendron assemblies to release DNA. Mass spectrometric assays demonstrate that the dendrons, as intended, do degrade under biologically relevant conditions over a period of hours. Multiscale modeling of degraded dendron structures suggests that complete dendron degradation would be required for DNA release. Importantly, in the presence of the lower pH associated with endosomes, or when bound to DNA, complete degradation of these dendrons becomes ineffective on the transfection time scale we propose this explains the poor transfection performance of these dendrons. As such, this paper demonstrates that taking this kind of multidisciplinary approach can yield a fundamental insight into the way in which dendrons can navigate barriers to cellular uptake. Lessons learned from this work will inform future dendron design for enhanced gene delivery.

  DOI：

  10.1021/ja2070736