Prop-2-ynyl 2-methyl-3-[2-methyl-3-[3-[methyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]propylcarbamoyloxy]-2-[3-[methyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]propylcarbamoyloxymethyl]propanoyl]oxy-2-[[2-methyl-3-[3-[methyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]propylcarbamoyloxy]-2-[3-[methyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]propylcarbamoyloxymethyl]propanoyl]oxymethyl]propanoate | 1351959-66-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Prop-2-ynyl 2-methyl-3-[2-methyl-3-[3-[methyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]propylcarbamoyloxy]-2-[3-[methyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]propylcarbamoyloxymethyl]propanoyl]oxy-2-[[2-methyl-3-[3-[methyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]propylcarbamoyloxy]-2-[3-[methyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]propylcarbamoyloxymethyl]propanoyl]oxymethyl]propanoate
• 英文别名: prop-2-ynyl 2-methyl-3-[2-methyl-3-[3-[methyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]propylcarbamoyloxy]-2-[3-[methyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]propylcarbamoyloxymethyl]propanoyl]oxy-2-[[2-methyl-3-[3-[methyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]propylcarbamoyloxy]-2-[3-[methyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]propylcarbamoyloxymethyl]propanoyl]oxymethyl]propanoate
• CAS: 1351959-66-4
• 化学式: C₇₀H₁₂₈N₁₂O₂₂
• 分子量: 1489.85
• InChiKey: NHMHYTPKRBVEQQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.12
• 重原子数：
  104.0
• 可旋转键数：
  48.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  398.5
• 氢给体数：
  8.0
• 氢受体数：
  26.0

反应信息

• 作为反应物：
  描述：

  N-(3-azidopropyl)dodecanamide 、 Prop-2-ynyl 2-methyl-3-[2-methyl-3-[3-[methyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]propylcarbamoyloxy]-2-[3-[methyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]propylcarbamoyloxymethyl]propanoyl]oxy-2-[[2-methyl-3-[3-[methyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]propylcarbamoyloxy]-2-[3-[methyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]propylcarbamoyloxymethyl]propanoyl]oxymethyl]propanoate 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 四氢呋喃 、 水 为溶剂， 以45%的产率得到
  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
• 作为产物：
  描述：

  Prop-2-ynyl 2-methyl-2-[[2-methyl-2-[(4-nitrophenoxy)carbonyloxymethyl]-3-phenoxycarbonyloxypropanoyl]oxymethyl]-3-[2-methyl-3-(4-nitrophenoxy)carbonyloxy-2-[(4-nitrophenoxy)carbonyloxymethyl]propanoyl]oxypropanoate 、 tert-butyl (3-((3-aminopropyl)(methyl)amino)propyl)carbamate 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 作用下， 生成 Prop-2-ynyl 2-methyl-3-[2-methyl-3-[3-[methyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]propylcarbamoyloxy]-2-[3-[methyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]propylcarbamoyloxymethyl]propanoyl]oxy-2-[[2-methyl-3-[3-[methyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]propylcarbamoyloxy]-2-[3-[methyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]propylcarbamoyloxymethyl]propanoyl]oxymethyl]propanoate
  参考文献：
  名称：

  WO2023/22926

  摘要：

  公开号：

文献信息

• Double-degradable responsive self-assembled multivalent arrays – temporary nanoscale recognition between dendrons and DNA
  作者：Anna Barnard、Paola Posocco、Maurizio Fermeglia、Ariane Tschiche、Marcelo Calderon、Sabrina Pricl、David K. Smith

  DOI：10.1039/c3ob42202j

  日期：——

  This article reports self-assembling dendrons which bind DNA in a multivalent manner. The molecular design directly impacts on self-assembly which subsequently controls the way these multivalent nanostructures bind DNA – this can be simulated by multiscale modelling. Incorporation of an S–S linkage between the multivalent hydrophilic dendron and the hydrophobic units responsible for self-assembly allows

  本文报道了以多价方式结合DNA的自组装树突。分子设计直接影响自组装，自组装随后可控制这些多价纳米结构结合DNA的方式-这可以通过多尺度建模来模拟。在多价亲水树突与负责自组装的疏水单元之间引入S–S键，可使这些结构发生触发的还原裂解，而二硫苏糖醇（DTT）诱导受控分解，从而释放结合的DNA。这样，高亲和力的自组装多价结合是暂时的。此外，由于多价树突是由酯构成的，因此第二个缓慢的降解步骤会导致这些结构的进一步分解。
• [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。
• [EN] DENDRITIC ARCHITECTURES AS NONVIRAL VECTORS IN GENE DELIVERY<br/>[FR] ARCHITECTURES DENDRITIQUES EN TANT QUE VECTEURS NON VIRAUX DANS LA DISTRIBUTION DE GÈNES
  申请人：[en]TIBA BIOTECH LLC

  公开号：WO2022212838A1

  公开（公告）日：2022-10-06

  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.
• NANOPARTICLE COMPOSITION FOR THE DELIVERY OF NUCLEIC ACID AGENTS
  申请人：Tiba Biotech LLC

  公开号：US20230310645A1

  公开（公告）日：2023-10-05

  The present disclosure relates to nanoparticle compositions for delivery of nucleic acid agents. The nanoparticle composition disclosed includes a carrier containing a dendritic polymer skeleton, a PEG moiety, an amine, and a hydrophobic unit. The size of the PEG moiety may be limited, potentially reducing or avoiding anti-PEG antibody induction.