Lipitoids - novel cationic lipids for cellular delivery of plasmid DNA in vitro
Lipitoids - novel cationic lipids for cellular delivery of plasmid DNA in vitro
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DOI：
10.1016/s1074-5521(98)90173-9
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发表时间：
1998-06-01
影响因子：
--
通讯作者：
Zuckermann, RN
中科院分区：
文献类型：
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作者：
Huang, CY;Uno, T;Zuckermann, RN
背景资料：虽然合成的非病毒载体有望用于质粒DNA的传递，但它们的基因转移效率远不能与病毒相匹配。为了系统地研究阳离子脂质的构效关系，合成了一个小型的阳离子脂质-类肽缀合物（类脂质）库。化合物进行了评估，他们的能力，形成复合物与质粒DNA和介导的DNA transfer in vitro.Results：脂质类肽共轭物方便地制备在高产量使用固相合成。几个lipitoids凝聚质粒DNA int 100 nm的球形颗粒和保护DNA从DNase消化，一个子集的lipitoids与一个重复的（氨乙基，中性，中性）侧链三聚体基序共轭与二肉豆蔻酰磷脂酰乙醇胺（DMPE）介导的DNA transfer with high-efficiency.Conclusions：自动固相合成的阳离子脂质允许快速合成的一组不同的转染试剂。最具活性的化合物DMPE-（Nae-Nmpe-Nmpe）（3）（Nae，N-氨乙基甘氨酸; Nmpe，N-对甲氧基苯乙基-甘氨酸）比脂质转染素或DMRIE-C（两种商业阳离子脂质转染试剂）更有效，并且在血清存在和不存在下都有活性。在血清存在下的活性表明在体内应用中是有效的。
Background: Although synthetic nonviral vectors hold promise for the delivery of plasmid DNA, their gene-transfer efficiencies are far from matching those of viruses. To systematically investigate the structure-activity relationship of cationic lipids, a small library of cationic lipid-peptoid conjugates (lipitoids) was synthesized. The compounds were evaluated for their ability to form complexes with plasmid DNA and to mediate DNA transfer in vitro.Results: Lipid-peptoid conjugates were conveniently prepared in high yield using solid-phase synthesis. Several lipitoids condensed plasmid DNA int 100 nm spherical particles and protected the DNA from DNase digestion, A subset of lipitoids with a repeated (aminoethyl, neutral, neutral) sidechain trimer motif conjugated with dimyristoyl phosphatidyl-ethanolamine (DMPE) mediate DNA transfer with high efficiency.Conclusions: Automated solid-phase synthesis of cationic lipids allowed the rapid synthesis of a diverse set of transfection reagents. The most active compound DMPE-(Nae-Nmpe-Nmpe)(3) (Nae, N-aminoethyl glycine; Nmpe, N-p-methoxyphenethyl-glycine) is more efficient than lipofectin or DMRIE-C (two commercial cationic lipid transfection reagents) and is active in the presence and absence of serum. The activity in the presence of serum suggests potent at for applications in vivo.