carbonic acid 2-(dimethylamino)ethyl ester 1-methyl-2-(methacryloylamino)ethyl ester

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机碳酸及其衍生物
• 英文名称: carbonic acid 2-(dimethylamino)ethyl ester 1-methyl-2-(methacryloylamino)ethyl ester
• 英文别名: 2-(Dimethylamino)ethyl 1-(2-methylprop-2-enoylamino)propan-2-yl carbonate
• 化学式: C₁₂H₂₂N₂O₄
• 分子量: 258.318
• InChiKey: IACZFGDEMMNUOV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  18
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  carbonic acid 2-(dimethylamino)ethyl ester 1-methyl-2-(methacryloylamino)ethyl ester 以 acetate buffer 为溶剂， 生成 N-(2-羟基丙基)甲基丙烯酰胺
  参考文献：
  名称：

  Polymer Side-Chain Degradation as a Tool to Control the Destabilization of Polyplexes

  摘要：

  Purpose. We purposed to design a cationic polymer that binds to pDNA to form polyplexes and that subsequently degrades within a few days at physiological pH and temperature, releasing the DNA in the cytosol of a cell.Methods. We synthesized a new monomer carbonic acid 2-dimethylaminoethyl ester 1-methyl-2-(2-methacryloylamino)-ethyl ester (abbreviated HPMA-DMAE) and the corresponding polymer. Hydrolysis of the carbonate ester of both the monomer and the polymer was investigated at 37degreesC. The DNA condensing properties of the pHPMA-DMAE was studied using dynamic light scattering (DLS) and zeta potential measurements. Degradation of the polyplexes at 37degreesC and pH 7.4 was monitored with DLS and gel electrophoresis. In vitro transfections were performed in COS-7 cell line.Results. pHPMA-DMAE is able to condense DNA into small particles (110 nm) with a positive zeta potential. The half-life of the polymer and monomer at 37degreesC and pH 7.4 was around 10 h whereas at pH 5, the half-life was 380 h. In line with this, due to hydrolysis of the side groups, pHPMA-DMAE-based polyplexes dramatically increased in size at 37degreesC and pH 7.4 whereas at pH 5.0, only a very small increase was observed. Interestingly, intact DNA was released from the polyplexes after 48 h at pH 7.4 whereas all DNA remained bound to the polymer at pH 5.0. Polyplexes were able to transfect cells with minimal cytotoxicity if the endosomal membrane-disrupting peptide INF-7 was added to the polyplex formulation.Conclusions. Degradation of the cationic side-chains of a polymer is a new tool for time-controlled release of DNA from polyplexes, preferably within the cytosol and/or nucleus.

  DOI：

  10.1023/b:pham.0000012165.68765.e6
• 作为产物：
  描述：

  2-(dimethylamino)ethyl imidazole-1-carboxylate 、 N-(2-羟基丙基)甲基丙烯酰胺 在 4-甲氧基苯酚 作用下， 以 二氯甲烷 为溶剂， 反应 120.0h， 生成 carbonic acid 2-(dimethylamino)ethyl ester 1-methyl-2-(methacryloylamino)ethyl ester 、 咪唑
  参考文献：
  名称：

  Polymer Side-Chain Degradation as a Tool to Control the Destabilization of Polyplexes

  摘要：

  Purpose. We purposed to design a cationic polymer that binds to pDNA to form polyplexes and that subsequently degrades within a few days at physiological pH and temperature, releasing the DNA in the cytosol of a cell.Methods. We synthesized a new monomer carbonic acid 2-dimethylaminoethyl ester 1-methyl-2-(2-methacryloylamino)-ethyl ester (abbreviated HPMA-DMAE) and the corresponding polymer. Hydrolysis of the carbonate ester of both the monomer and the polymer was investigated at 37degreesC. The DNA condensing properties of the pHPMA-DMAE was studied using dynamic light scattering (DLS) and zeta potential measurements. Degradation of the polyplexes at 37degreesC and pH 7.4 was monitored with DLS and gel electrophoresis. In vitro transfections were performed in COS-7 cell line.Results. pHPMA-DMAE is able to condense DNA into small particles (110 nm) with a positive zeta potential. The half-life of the polymer and monomer at 37degreesC and pH 7.4 was around 10 h whereas at pH 5, the half-life was 380 h. In line with this, due to hydrolysis of the side groups, pHPMA-DMAE-based polyplexes dramatically increased in size at 37degreesC and pH 7.4 whereas at pH 5.0, only a very small increase was observed. Interestingly, intact DNA was released from the polyplexes after 48 h at pH 7.4 whereas all DNA remained bound to the polymer at pH 5.0. Polyplexes were able to transfect cells with minimal cytotoxicity if the endosomal membrane-disrupting peptide INF-7 was added to the polyplex formulation.Conclusions. Degradation of the cationic side-chains of a polymer is a new tool for time-controlled release of DNA from polyplexes, preferably within the cytosol and/or nucleus.

  DOI：

  10.1023/b:pham.0000012165.68765.e6

文献信息

• Polymer Side-Chain Degradation as a Tool to Control the Destabilization of Polyplexes
  作者：Arjen M. Funhoff、Cornelus F. van Nostrum、Adriënne P. C. A. Janssen、Marcel H. A. M. Fens、Daan J. A. Crommelin、Wim E. Hennink

  DOI：10.1023/b:pham.0000012165.68765.e6

  日期：2004.1

  Purpose. We purposed to design a cationic polymer that binds to pDNA to form polyplexes and that subsequently degrades within a few days at physiological pH and temperature, releasing the DNA in the cytosol of a cell.Methods. We synthesized a new monomer carbonic acid 2-dimethylaminoethyl ester 1-methyl-2-(2-methacryloylamino)-ethyl ester (abbreviated HPMA-DMAE) and the corresponding polymer. Hydrolysis of the carbonate ester of both the monomer and the polymer was investigated at 37degreesC. The DNA condensing properties of the pHPMA-DMAE was studied using dynamic light scattering (DLS) and zeta potential measurements. Degradation of the polyplexes at 37degreesC and pH 7.4 was monitored with DLS and gel electrophoresis. In vitro transfections were performed in COS-7 cell line.Results. pHPMA-DMAE is able to condense DNA into small particles (110 nm) with a positive zeta potential. The half-life of the polymer and monomer at 37degreesC and pH 7.4 was around 10 h whereas at pH 5, the half-life was 380 h. In line with this, due to hydrolysis of the side groups, pHPMA-DMAE-based polyplexes dramatically increased in size at 37degreesC and pH 7.4 whereas at pH 5.0, only a very small increase was observed. Interestingly, intact DNA was released from the polyplexes after 48 h at pH 7.4 whereas all DNA remained bound to the polymer at pH 5.0. Polyplexes were able to transfect cells with minimal cytotoxicity if the endosomal membrane-disrupting peptide INF-7 was added to the polyplex formulation.Conclusions. Degradation of the cationic side-chains of a polymer is a new tool for time-controlled release of DNA from polyplexes, preferably within the cytosol and/or nucleus.