Molecular design of amphiphiles with DNA transfer ability into cell

阳离子两亲物具有铵头、烃尾和谷氨酸连接子，亚甲基间隔子，已被用于将DNA递送到真核细胞。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之间的关系：1.我们发现一种二烷基铵两亲物，双十二烷基N- [ p-（2-三甲基铵乙氧基）苯甲酰基] -L-谷氨酸溴化物的DNA转染率高于市售脂质DOTMA，两亲性化合物的转基因效率与其理化性质有很好的相关性，2.设计了一种新的阳离子两亲分子，并合成了一种新的阳离子两亲分子; 3.研究了阳离子两亲分子与DNA的结构相互作用，通过电子显微镜，CD和NMR光谱，和荧光透视。在间隔区含有亚苯基的两亲分子通过与DNA结合而限制了它们的移动性，而其他两亲分子则具有足够的柔性，可以沿沿着DNA螺旋排列。另一方面，在低于它们的Tc的温度下，形成双层的两亲物迫使DNA构象发生变化。

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.