Institute of Pharmacy, Department of Biochemical Pharmacy, Martin-Luther-University Halle-Wittenberg, Wolfgang-Langenbeck-Strasse 4, 06120 Halle (Saale), Germany.
Int J Pharm. 2011 May 16;409(1-2):46-56. doi: 10.1016/j.ijpharm.2011.02.022. Epub 2011 Feb 25.
Malonic acid diamides with two long hydrophobic alkyl chains and a basic polar head group as a new class of non-viral gene transferring compounds have shown high transfection efficiency and moderate toxicity. Based on the results obtained with saturated and unsaturated alkyl residues new derivatives with a more complex head group structure have been synthesized. For this purpose, cationic respectively basic groups were introduced by one or two lysine residues bound via tris(aminoethyl)amine spacer to the malonic acid diamide backbone. By studying in vitro gene delivery an increase of transfection efficacy was observed when using lipids with at least one unsaturated alkyl chain. This leads to cationic lipids exhibiting comparable or even higher transfection efficacies compared to the commercially available transfection agents LipofectAmine™ and SuperFect™. Phase transitions and phase structures of selected compounds have been analyzed and discussed in terms of transfection abilities. Particle size and zeta potential of liposomes and lipoplexes were also determined.
具有两个长疏水烷基链和一个碱性极性头基的丙二酸二酰胺作为一类新的非病毒基因转染化合物，表现出了高转染效率和中等毒性。基于饱和和不饱和烷基残基的研究结果，我们已经合成了具有更复杂的头基结构的新衍生物。为此，通过三(氨基乙基)胺间隔臂将一个或两个赖氨酸残基结合到丙二酸二酰胺主链上，引入了阳离子基团或碱性基团。通过体外基因传递研究，当使用至少一个不饱和烷基链的脂质时，观察到转染效率的增加。这导致阳离子脂质的转染效率与商业上可获得的转染试剂 LipofectAmine™ 和 SuperFect™ 相当，甚至更高。根据转染能力，分析和讨论了选定化合物的相转变和相结构。还测定了脂质体和脂质体的粒径和 Zeta 电位。
