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Molecular design of amphiphiles with DNA transfer ability into cell

具有 DNA 转移能力的两亲物的分子设计

基本信息

批准号：
04558023
负责人：
ITO Akio
金额：
$ 2.62万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04558023/
关键词：
Synthetic bilayr membrane Liposome DNA transfection DNA-liposome interaction リポソ-ム

项目摘要

Cationic amphiphiles which have aquaternary ammonium head, hydrocarbon tailsanda glutamic acid connector with methylenespacer have been used for delivery ofDNA into eukaryotic cells. we studied thecorrelation between the efficiency ofvarious cationic amphiphiles in DNA transfection and their physicochemical properties1.We found that one of dialkyl ammonium amphiphile, didodecyl N- [ p- ( 2-trimethylammonioethoxy ) benzoyl ] -L-glutamate bromide, had a higher DNA transfection than commercially available lipid, DOTMA,and that there was a good correlation between their efficiencies in gene transfer and physicochemical characteristics.Amphiphilic compounds tthe phase transition temperatures ( Tc )of which are lower than the culture temperature and which form small stable vesicles are good carriers of DNA into cultured cells.2.The result makes it possible to design compounds with a more efficient DNA transfection ability, and we designed and obtained a new cationic amphiphile with higher activity.3.We investigated interaction the structural between cationic amphiphilesandDNA,bymeans of electron microscopy, CDandNMRspectroscopies, and fluoroscopy. Amphiphiles with phenylene in the spacer regionare restricted their mobility by bindingwith DNA while others are flexibleenough for arranging along DNA helix. Ontheother hand, conformation of DNA is forced to change by bilayr-forming amphiphiles at lower temperature than their Tc's.

具有季铵头部、烃尾和带有亚甲基间隔基的谷氨酸连接器的阳离子两亲物已被用于将DNA递送至真核细胞中。我们研究了各种阳离子两亲物在DNA转染中的效率与其理化性质的相关性1。我们发现二烷基铵两亲物之一双十二烷基N-[对(2-三甲基氨基乙氧基)苯甲酰基]-L-谷氨酸溴化物比市售脂质具有更高的DNA转染率， DOTMA，并且它们的基因转移效率和理化特性之间存在良好的相关性。相变温度（Tc）低于培养温度并形成稳定的小囊泡的两亲性化合物是DNA进入培养细胞的良好载体。2.该结果使得设计具有更高效的DNA转染能力的化合物成为可能，我们设计并获得了一种新的阳离子 3.通过电子显微镜、CD和NMR光谱以及荧光透视研究了阳离子两亲物与DNA之间的结构相互作用。间隔区带有亚苯基的两亲物通过与 DNA 结合而限制其移动性，而其他两亲物则足够灵活，可以沿着 DNA 螺旋排列。另一方面，双层形成的两亲物在低于其 Tc 的温度下迫使 DNA 的构象发生变化。