N-2-[N'-(N^ε-tert-butyloxycarbonyl-L-Lys-N^ε-tert-butyloxycarbonyl-L-Lys)]aminoethyl-N,N-di-n-tetradecylamine | 678975-71-8

• 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: N-2-[N'-(N^ε-tert-butyloxycarbonyl-L-Lys-N^ε-tert-butyloxycarbonyl-L-Lys)]aminoethyl-N,N-di-n-tetradecylamine
• CAS: 678975-71-8
• 化学式: C₅₂H₁₀₄N₆O₆
• 分子量: 909.434
• InChiKey: NFLVUZPOXIHRIR-ZYBCLOSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.01
• 重原子数：
  64.0
• 可旋转键数：
  42.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  164.12
• 氢给体数：
  5.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  N-2-[N'-(N^ε-tert-butyloxycarbonyl-L-Lys-N^ε-tert-butyloxycarbonyl-L-Lys)]aminoethyl-N,N-di-n-tetradecylamine 在 N-羟基丁二酰亚胺 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成 N,N-di-n-tetradecyl-N-methyl-N-2-[N'-(L-Lysyl)₃]aminoethylammonium trifluoroacetate
  参考文献：
  名称：

  Design, Syntheses and In Vitro Gene Delivery Efficacies of Novel Mono-, Di- and Trilysinated Cationic Lipids:  A Structure−Activity Investigation

  摘要：

  Structure-activity investigation including design, syntheses, and evaluation of relative in vitro gene delivery efficacies of a novel series of cationic amphiphiles (1-10) containing mono-, di-, and trilysine headgroups are described in CHO, COS-1, and HepG2 cells. Several interesting and rather unexpected transfection profiles were observed. In general, lipid 1 with the myristyl tail used in combination with DOPE as colipid exhibited superior transfection properties compared to (a) the monolysinated analogues with longer hydrocarbon tails (lipids 2-4), (b) the dilysine (lipids 5-7) and the trilysine headgroup analogues (lipids 8-10), and (c) commercially available LipofectAmine with multiple positive charges in its polar region. As a preliminary estimate of the relative DNA-compacting efficacies of these new lysinated cationic lipids, the hydrodynamic diameters of representative lipoplexes were measured using dynamic laser light scattering technique. Our lipoplex size data are consistent with the notion that covalent grafting of an increasing number of positively charged functional groups in the headgroup region of cationic lipids need not necessarily result in more compacted lipoplexes. Both gel retardation and DNase I sensitivity assays indicated similar lipid/DNA binding interactions for all the novel mono-, di-, and trilysinated cationic lipids. MTT-assay-based cell viability results clearly demonstrate that the overall lower transfection properties of trilysine analogues (8-10) compared to their mono- (1-4) and dilysinated (5-7) counterparts are unlikely to originate from differential toxicity related effects. Taken together, the present findings support the notion that caution needs to be exercised in ensuring enhanced gene delivery efficacies of cationic lipids through covalent grafting of multiple lysine functionalities in the headgroup region.

  DOI：

  10.1021/jm030541+
• 作为产物：
  描述：

  N-2-[N'-(N^α-benzyloxycarbonyl,N^ε-tert-butyloxycarbonyl-L-Lys-N^ε-tert-butyloxycarbonyl-L-Lys)]aminoethyl-N,N-di-n-tetradecylamine 在 palladium on activated charcoal ammonium formate 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以81.9%的产率得到N-2-[N'-(N^ε-tert-butyloxycarbonyl-L-Lys-N^ε-tert-butyloxycarbonyl-L-Lys)]aminoethyl-N,N-di-n-tetradecylamine
  参考文献：
  名称：

  Design, Syntheses and In Vitro Gene Delivery Efficacies of Novel Mono-, Di- and Trilysinated Cationic Lipids:  A Structure−Activity Investigation

  摘要：

  Structure-activity investigation including design, syntheses, and evaluation of relative in vitro gene delivery efficacies of a novel series of cationic amphiphiles (1-10) containing mono-, di-, and trilysine headgroups are described in CHO, COS-1, and HepG2 cells. Several interesting and rather unexpected transfection profiles were observed. In general, lipid 1 with the myristyl tail used in combination with DOPE as colipid exhibited superior transfection properties compared to (a) the monolysinated analogues with longer hydrocarbon tails (lipids 2-4), (b) the dilysine (lipids 5-7) and the trilysine headgroup analogues (lipids 8-10), and (c) commercially available LipofectAmine with multiple positive charges in its polar region. As a preliminary estimate of the relative DNA-compacting efficacies of these new lysinated cationic lipids, the hydrodynamic diameters of representative lipoplexes were measured using dynamic laser light scattering technique. Our lipoplex size data are consistent with the notion that covalent grafting of an increasing number of positively charged functional groups in the headgroup region of cationic lipids need not necessarily result in more compacted lipoplexes. Both gel retardation and DNase I sensitivity assays indicated similar lipid/DNA binding interactions for all the novel mono-, di-, and trilysinated cationic lipids. MTT-assay-based cell viability results clearly demonstrate that the overall lower transfection properties of trilysine analogues (8-10) compared to their mono- (1-4) and dilysinated (5-7) counterparts are unlikely to originate from differential toxicity related effects. Taken together, the present findings support the notion that caution needs to be exercised in ensuring enhanced gene delivery efficacies of cationic lipids through covalent grafting of multiple lysine functionalities in the headgroup region.

  DOI：

  10.1021/jm030541+