(1-{4-[15-(2-aminoethylcarbamoyl)pentadecyloxy]phenylcarbamoyl}-4-tert-butoxycabonylaminobutyl)carbamic acid tert-butyl ester | 1254581-05-9

• 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: (1-{4-[15-(2-aminoethylcarbamoyl)pentadecyloxy]phenylcarbamoyl}-4-tert-butoxycabonylaminobutyl)carbamic acid tert-butyl ester
• CAS: 1254581-05-9
• 化学式: C₃₉H₆₉N₅O₇
• 分子量: 720.006
• InChiKey: FAAIRNJJOFMISB-XIFFEERXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.74
• 重原子数：
  51.0
• 可旋转键数：
  26.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  170.11
• 氢给体数：
  5.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  (1-{4-[15-(2-aminoethylcarbamoyl)pentadecyloxy]phenylcarbamoyl}-4-tert-butoxycabonylaminobutyl)carbamic acid tert-butyl ester 、 葡萄糖酸内酯 在 N,N-二异丙基乙胺 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以90%的产率得到[4-tert-butoxylamino-4-(4-{15-[2-(2,3,4,5,6-pentahydroxyhexanoylamino)ethylcabamoyl]pentadecyloxy}phenylcarbamoyl)butyl]carbamic acid tert-butyl ester
  参考文献：
  名称：

  New Unsymmetrical Bolaamphiphiles: Synthesis, Assembly with DNA, and Application for Gene Delivery

  摘要：

  The success in gene therapy relies strongly on new efficient gene delivery vectors. Nonviral vectors based on lipids and polymers constitute an important alternative to the viral vectors. However, the key problem with these vectors is the poor structural control of their DNA complexes. In the present work, following new design we synthesized unsymmetrical bolaamphiphiles, molecules bearing neutral sugar (gluconic acid) and dicationic ornithine head groups connected by different long hydrophobic spacers. Within this design, a positively charged headgroup is expected to bind DNA, the hydrophobic spacer is to drive the formation of a monolayer membrane shell around DNA, while the neutral group is to be exposed outside of the complex. Our fluorescence and gel electrophoresis data showed that self-assembly of bolas and their interaction with DNA depend strongly on the bola structure. The size of bola/DNA complexes (bolaplexes) estimated from dynamic light scattering data was similar to 100 nm at low N/P (cationic nitrogen/DNA phosphate molar ratio), while at higher N/Ps it was significantly larger due to neutralization of their surface charge. Atomic force microscopy studies revealed nanostructural rod-shaped or spherical morphology of the bolaplexes. Transfection efficiency of the bolaplexes in vitro was significant when either DOPE or chloroquine were used as helping agents, suggesting that the key barrier for their internalization is the endosomal escape. Finally, all bolas showed low cytotoxicity (cell viability >80%). The present results show that bolas are prospective candidates for construction of nonviral gene delivery vectors. We believe that further optimization of polar head groups and a hydrophobic spacer in the bolas will lead to vectors with controlled small size and high transfection efficiency.

  DOI：

  10.1021/bc100334t
• 作为产物：
  描述：

  对氨基苯酚 在 水 、 potassium carbonate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 103.0h， 生成 (1-{4-[15-(2-aminoethylcarbamoyl)pentadecyloxy]phenylcarbamoyl}-4-tert-butoxycabonylaminobutyl)carbamic acid tert-butyl ester
  参考文献：
  名称：

  New Unsymmetrical Bolaamphiphiles: Synthesis, Assembly with DNA, and Application for Gene Delivery

  摘要：

  The success in gene therapy relies strongly on new efficient gene delivery vectors. Nonviral vectors based on lipids and polymers constitute an important alternative to the viral vectors. However, the key problem with these vectors is the poor structural control of their DNA complexes. In the present work, following new design we synthesized unsymmetrical bolaamphiphiles, molecules bearing neutral sugar (gluconic acid) and dicationic ornithine head groups connected by different long hydrophobic spacers. Within this design, a positively charged headgroup is expected to bind DNA, the hydrophobic spacer is to drive the formation of a monolayer membrane shell around DNA, while the neutral group is to be exposed outside of the complex. Our fluorescence and gel electrophoresis data showed that self-assembly of bolas and their interaction with DNA depend strongly on the bola structure. The size of bola/DNA complexes (bolaplexes) estimated from dynamic light scattering data was similar to 100 nm at low N/P (cationic nitrogen/DNA phosphate molar ratio), while at higher N/Ps it was significantly larger due to neutralization of their surface charge. Atomic force microscopy studies revealed nanostructural rod-shaped or spherical morphology of the bolaplexes. Transfection efficiency of the bolaplexes in vitro was significant when either DOPE or chloroquine were used as helping agents, suggesting that the key barrier for their internalization is the endosomal escape. Finally, all bolas showed low cytotoxicity (cell viability >80%). The present results show that bolas are prospective candidates for construction of nonviral gene delivery vectors. We believe that further optimization of polar head groups and a hydrophobic spacer in the bolas will lead to vectors with controlled small size and high transfection efficiency.

  DOI：

  10.1021/bc100334t