胆固醇-TEG叠氮化物 | 1391826-58-6

• 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
• 中文名称: 胆固醇-TEG叠氮化物
• 英文名称: N-{{[(azidoethoxy)ethoxy]ethoxy}ethyl}cholest-5-en-3-ylcarbamate
• 英文别名: Cholesteryl-TEG azide；[(3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl] N-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethyl]carbamate
• CAS: 1391826-58-6
• 化学式: C₃₆H₆₂N₄O₅
• 分子量: 630.912
• InChiKey: POWZASPNLQFLJO-MKQVXYPISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.4
• 重原子数：
  45
• 可旋转键数：
  19
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  80.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  胆固醇-TEG叠氮化物 、 在 乙酸–三乙胺 、 sodium ascorbate 作用下， 以 水 、 二甲基亚砜 为溶剂， 生成
  参考文献：
  名称：

  通过与小分子缀合进行二核苷酸的细胞递送：抗癌应用的靶向翻译起始

  摘要：

  靶向帽依赖性翻译起始是可能导致新型抗癌疗法开发的实验方法之一。合成二核苷 5',5'-三磷酸帽类似物是体外真核翻译起始因子 4E (eIF4E) 的有效拮抗剂，可以抵消癌细胞中 eIF4E 水平升高；然而，将这些化合物转化为治疗剂仍然具有挑战性——它们不容易渗透到细胞中，并且容易受到酶促裂解。在这里，我们测试了几种小分子配体（叶酸、生物素、葡萄糖和胆固醇）将可水解和抗裂解帽类似物递送到细胞中的潜力。使用模型荧光探针和帽子-配体缀合物进行的广泛结构-活性关系 (SAR) 研究表明，胆固醇极大地促进帽子类似物的摄取，而不干扰与 eIF4E 的相互作用。鉴定出的最有效的胆固醇缀合物对癌细胞表现出凋亡介导的细胞毒性。

  DOI：

  10.1039/d1sc02143e
• 作为产物：
  描述：

  胆固醇 、 1-氨基-11-叠氮-3,6,9-三氧杂十一烷 、 N,N'-羰基二咪唑 以 二氯甲烷 、 氯仿 为溶剂， 生成 胆固醇-TEG叠氮化物
  参考文献：
  名称：

  [EN] ANANDAMIDE-MODIFIED NUCLEIC ACID MOLECULES
  [FR] MOLÉCULES D'ACIDE NUCLÉIQUE MODIFIÉS PAR L'ANANDAMIDE

  摘要：

  本发明涉及一种共轭物，其中至少包含一个多不饱和脂肪酸残基，特别是一种花生四烯酸残基，更具体地说是一种花生四烯酸酰乙醇胺（anandamide）残基，并且至少与之共价结合的是从核酸、核苷和核苷酸中选择的至少一个核苷酸组分。这种共轭物适用于高效转染哺乳动物细胞，包括人类细胞。因此，提供了一种用于传递治疗分子的新载体，包括反义分子、siRNA分子、miRNA分子、antagomirs或这些分子的前体，以及治疗性核苷或核苷酸。

  公开号：

  WO2014009429A1

文献信息

• Multimeric oligonucleotide compounds
  申请人：Translate Bio MA, Inc.

  公开号：US10704046B2

  公开（公告）日：2020-07-07

  The disclosure provides multimeric oligonucleotide compounds, comprising two or more target-specific oligonucleotides (e.g., antisense oligonucleotides (ASOs)), each being resistant to cleavage, and linked together by a cleavable linker. In particular, two or more linked target-specific oligonucleotides, each to a different target, allows concomitant inhibition of multiple genes' expression levels, while exhibiting favorable pharmacokinetic and pharmacodynamic properties. Methods of making and uses of the described compounds are also provided.

  本公开提供了多聚物寡核苷酸化合物，包括两个或多个靶向特异性寡核苷酸（如反义寡核苷酸（ASO）），每个寡核苷酸都具有抗裂解性，并通过可裂解连接体连接在一起。特别是两个或更多链接的靶标特异性寡核苷酸，每个都针对不同的靶标，可以同时抑制多个基因的表达水平，同时表现出良好的药代动力学和药效学特性。还提供了所述化合物的制造方法和用途。
• Multimeric oligonucleotide compounds having non-nucleotide based cleavable linkers
  申请人：Translate Bio MA, Inc.

  公开号：US10844375B2

  公开（公告）日：2020-11-24

  The disclosure provides multimeric oligonucleotide compounds, comprising two or more target-specific oligonucleotides (e.g., antisense oligonucleotides (ASOs)), each being resistant to cleavage, and linked together by a cleavable linker. In particular, two or more linked target-specific oligonucleotides, each to a different target, allows concomitant inhibition of multiple genes' expression levels, while exhibiting favorable pharmacokinetic and pharmacodynamic properties. Methods of making and uses of the described compounds are also provided.

  本公开提供了多聚物寡核苷酸化合物，包括两个或多个靶向特异性寡核苷酸（如反义寡核苷酸（ASO）），每个寡核苷酸都具有抗裂解性，并通过可裂解连接体连接在一起。特别是两个或更多链接的靶标特异性寡核苷酸，每个都针对不同的靶标，可以同时抑制多个基因的表达水平，同时表现出良好的药代动力学和药效学特性。还提供了所述化合物的制造方法和用途。
• Click-Modified Anandamide siRNA Enables Delivery and Gene Silencing in Neuronal and Immune Cells
  作者：Julian Willibald、Johannes Harder、Konstantin Sparrer、Karl-Klaus Conzelmann、Thomas Carell

  DOI：10.1021/ja303251f

  日期：2012.8.1

  Click chemistry of alkyne-modified RNA with different receptor ligand azides was used to prepare 3'-folate, 3'-cholesterol, and, as a new entity, 3'-anandamide-modified RNA in high yields and excellent purity. The anandamide-modified RNA shows surprisingly high transfection properties and enables the delivery of siRNA even into difficult-to-transfect RBL-2H3 cells which model neuronal uptake. Furthermore, the system was employed in human immune cells (BJAB), demonstrating silencing effects similar to those of a cationic, benchmark transfection reagent. In addition, the anandamide conjugates were found to be nontoxic. The reported chemistry and the described properties of the anandamide siRNA extend the possibilities of using siRNA-based gene silencing in neuronal and immune cells.
• MULTIMERIC OLIGONUCLEOTIDE COMPOUNDS
  申请人：RANA THERAPEUTICS, INC.

  公开号：US20150247141A1

  公开（公告）日：2015-09-03

  The disclosure provides multimeric oligonucleotide compounds, comprising two or more target-specific oligonucleotides (e.g., antisense oligonucleotides (ASOs)), each being resistant to cleavage, and linked together by a cleavable linker. In particular, two or more linked target-specific oligonucleotides, each to a different target, allows concomitant inhibition of multiple genes' expression levels, while exhibiting favorable pharmacokinetic and pharmacodynamic properties. Methods of making and uses of the described compounds are also provided
• MULTIMERIC OLIGONUCLEOTIDES COMPOUNDS
  申请人：Uhlmann Eugen

  公开号：US20150299695A1

  公开（公告）日：2015-10-22

  The disclosure provides multimeric oligonucleotide compounds, comprising two or more target-specific oligonucleotides (e.g., antisense oligonucleotides (ASOs)), each being resistant to cleavage, and linked together by a cleavable linker. In particular, two or more linked target-specific oligonucleotides, each to a different target, allows concomitant inhibition of multiple genes' expression levels, while exhibiting favorable pharmacokinetic and pharmacodynamic properties. Methods of making and uses of the described compounds are also provided.