Prop-2-ynyl 2-methyl-3-[2-methyl-3-(4-nitrophenoxy)carbonyloxy-2-[(4-nitrophenoxy)carbonyloxymethyl]propanoyl]oxy-2-[[2-methyl-3-(4-nitrophenoxy)carbonyloxy-2-[(4-nitrophenoxy)carbonyloxymethyl]propanoyl]oxymethyl]propanoate | 1351959-64-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Prop-2-ynyl 2-methyl-3-[2-methyl-3-(4-nitrophenoxy)carbonyloxy-2-[(4-nitrophenoxy)carbonyloxymethyl]propanoyl]oxy-2-[[2-methyl-3-(4-nitrophenoxy)carbonyloxy-2-[(4-nitrophenoxy)carbonyloxymethyl]propanoyl]oxymethyl]propanoate
• CAS: 1351959-64-2
• 化学式: C₄₆H₄₀N₄O₂₆
• 分子量: 1064.83
• InChiKey: DJERDTPQQVUJIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.76
• 重原子数：
  76.0
• 可旋转键数：
  24.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  393.58
• 氢给体数：
  0.0
• 氢受体数：
  26.0

反应信息

• 作为反应物：
  描述：

  Prop-2-ynyl 2-methyl-3-[2-methyl-3-(4-nitrophenoxy)carbonyloxy-2-[(4-nitrophenoxy)carbonyloxymethyl]propanoyl]oxy-2-[[2-methyl-3-(4-nitrophenoxy)carbonyloxy-2-[(4-nitrophenoxy)carbonyloxymethyl]propanoyl]oxymethyl]propanoate 、 N,N-二甲基乙二胺 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以90 %的产率得到
  参考文献：
  名称：

  [EN] DENDRITIC ARCHITECTURES AS NONVIRAL VECTORS IN GENE DELIVERY
  [FR] ARCHITECTURES DENDRITIQUES EN TANT QUE VECTEURS NON VIRAUX DANS LA DISTRIBUTION DE GÈNES

  摘要：

  Disclosed herein are novel dendritic structures that can be used in combination with other lipid components to form nanoparticles with nucleic acids, to facilitate the intracellular delivery of nucleic acids bothin vitroandin vivo. Nanoparticle compositions comprising the compounds and methods for their use for treating or preventing diseases or conditions are also provided.

  公开号：

  WO2022212838A1
• 作为产物：
  描述：

  prop-2-yn-1-yl 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate 在 吡啶 、 4-二甲氨基吡啶 、 硫酸 作用下， 以 吡啶 、 甲醇 、 二氯甲烷 为溶剂， 生成 Prop-2-ynyl 2-methyl-3-[2-methyl-3-(4-nitrophenoxy)carbonyloxy-2-[(4-nitrophenoxy)carbonyloxymethyl]propanoyl]oxy-2-[[2-methyl-3-(4-nitrophenoxy)carbonyloxy-2-[(4-nitrophenoxy)carbonyloxymethyl]propanoyl]oxymethyl]propanoate
  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

文献信息

• [EN] CARRIERS FOR EFFICIENT NUCLEIC ACID DELIVERY<br/>[FR] VECTEURS DESTINÉS À L'ADMINISTRATION EFFICACE D'ACIDES NUCLÉIQUES
  申请人：TIBA BIOTECH LLC

  公开号：WO2021207020A1

  公开（公告）日：2021-10-14

  Nanoparticle compositions for delivery of nucleic acids to subjects including carriers comprising polyester (PE) dendrimers or dendrons, and therapeutic or immunogenic nucleic acid agents enclosed within the PE are described. Methods for treating or preventing diseases or conditions in a subject by administering the nanoparticle compositions that provide immune responses and synergistic therapeutic or preventive effects are provided.

  描述了用于将核酸传递给受试者的纳米颗粒组合物，其中包括包含聚酯（PE）树状聚合物或树状分子的载体，以及包含在PE内部的治疗性或免疫原性核酸药剂。提供了通过给予提供免疫反应和协同治疗或预防效果的纳米颗粒组合物来治疗或预防受试者疾病或状况的方法。