含大环多胺的两亲性小分子的设计合成及与DNA的相互作用

Cyclen-based Cationic Lipids:Design,Synthesis and Interactions with DNA

设计合成了2个含大环多胺亲水基团和甾体亲脂结构的两亲性小分子化合物,其结构经核磁共振谱、红外光谱和高分辨质谱确证.凝胶电泳实验结果表明,此类化合物与Sn-甘油-1,2-二油酰-3-磷酰乙醇胺(DOPE)形成的阳离子脂质体对DNA有很强的包裹能力.两种脂质体M1和M2分别在N/P摩尔比为7和5时即可完全包裹质粒DNA.另外,此类脂质体与DNA形成的复合物的粒径为160～220 nm,Zeta电位为20～40 mV.结果表明,此类脂质体具备了作为非病毒基因载体的潜在性,可为设计阳离子脂质提供新思路.

The clinical success of gene therapy requires a safe and effective gene delivery system.Cationic lipids have particularly excellent potential for gene delivery applications because of their lesser immunogenic nature,ability to deliver large pieces of DNA,and ease of handling and preparation techniques.In this work,two cyclen-based amphiphilic molecules including steroid moieties were designed and synthesized,and their structures were characterized by 1H NMR,IR and HRMS.Cationic liposomes were prepared by mixing the molecules with DOPE.Agarose gel electrophoresis demonstrates that the liposomes M1 and M2 could condense plasmid DNA at N/P molar ratios of 7 and 5,respectively.The sizes of the formed lipoplexes were measured to be around 160—220 nm,while the zeta-potentials of the lipoplexes were found to be 20—40 mV,suggesting that the synthesized cationic lipids might be of great potential as non-viral gene carrier.