Hydrophobic moiety of cationic lipids strongly modulates their transfection activity.
Hydrophobic moiety of cationic lipids strongly modulates their transfection activity.
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DOI：
10.1021/mp8002573
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发表时间：
2009-05
影响因子：
4.9
通讯作者：
Macdonald RC
中科院分区：
文献类型：
--
作者：
Koynova R;Tenchov B;Wang L;Macdonald RC
合成阳离子脂质体是广泛使用的非病毒基因载体的组分，并且调节其转染效率的因素是相当感兴趣的主题。鉴于与聚阴离子核酸的静电相互作用在形成脂质复合物中发挥的重要作用，改善转染的常见经验方法是合成和测试具有带正电荷的极性基团的新版本的两亲物，而很少关注疏水脂质部分的作用。~20阳离子磷脂酰胆碱（PC）衍生物的数据的基础上，在这里，我们表明，这些脂质的烃链的变化调制超过两个数量级的转染效率。所观察到的分子结构-活性关系表现为活性对两个重要分子特征-链不饱和度和脂质链中的碳原子总数的良好表达的依赖性，其代表脂质疏水体积和亲脂-亲脂比。转染率随链长的减小和链不饱和度的增加而增加。最大的转染被发现与单不饱和14：1链的阳离子PC。特别重要的是，高转染脂质强烈促进两性离子膜磷脂酰乙醇胺（PE）中的立方相形成。这些显着的相关性指向一个替代的，链依赖性的转染过程中，不相关的静电阳离子-阴离子脂质相互作用。
Synthetic cationic lipids are widely used component of non-viral gene carriers and the factors regulating their transfection efficiency are subject of considerable interest. In view of the important role that electrostatic interactions with the polyanionic nucleic acids play in formation of lipoplexes, a common empirical approach to improving transfection has been the synthesis and testing of amphiphiles with new versions of positively charged polar groups, while much less attention has been given to the role of the hydrophobic lipid moieties. On basis of data for ~20 cationic phosphatidylcholine (PC) derivatives, here we demonstrate that hydrocarbon chain variations of these lipids modulate by over two orders of magnitude their transfection efficiency. The observed molecular structure-activity relationship manifests in well expressed dependences of activity on two important molecular characteristics - chain unsaturation and total number of carbon atoms in the lipid chains, which is representative of the lipid hydrophobic volume and hydrophilic-lipophilic ratio. Transfection increases with decrease of chain length and increase of chain unsaturation. Maximum transfection was found for cationic PCs with monounsaturated 14:1 chains. It is of particular importance that the high-transfection lipids strongly promote cubic phase formation in zwitterionic membrane phosphatidylethanolamine (PE). These remarkable correlations point to an alternative, chain-dependent process in transfection, not related to the electrostatic cationic-anionic lipid interactions.
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影响因子：
3.8
作者：
MacDonald, RC;Rakhmanova, VA;Lahiri, MK
通讯作者：
Lahiri, MK
DOI：
10.1016/0005-2736(90)90017-i
发表时间：
1990-03-30
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
LEVENTIS, R;SILVIUS, JR
通讯作者：
SILVIUS, JR
影响因子：
3.4
作者：
Koynova, Rumiana;Tarahovsky, Yury S.;MacDonald, Robert C.
通讯作者：
MacDonald, Robert C.
影响因子：
4.7
作者：
Koynova, R;Wang, L;MacDonald, RC
通讯作者：
MacDonald, RC
影响因子：
3.4
作者：
Koynova, Rumiana;MacDonald, Robert C.
通讯作者：
MacDonald, Robert C.