通过硫代胆固醇修饰将2'-O-甲基寡核糖核苷酸有效掺入脂质体并增强细胞结合。
Effective incorporation of 2'-O-methyl-oligoribonucleotides into liposomes and enhanced cell association through modification with thiocholesterol.
作者信息
Oberhauser B, Wagner E
机构信息
Institute of Molecular Pathology, Vienna, Austria.
出版信息
Nucleic Acids Res. 1992 Feb 11;20(3):533-8. doi: 10.1093/nar/20.3.533.
Abstract
Cholesterol was linked to 2'-O-methyl-oligoribonucleotides (2'-OMe-RNA) via a disulfide bond by reacting the 3'-(pyridyldithio)-modified 2'-OMe-RNA with thiocholesterol in dichloromethane-methanol solution. This ligation reaction was made possible by a novel strategy in which the highly charged oligonucleotide was rendered soluble in nonaqueous solvent through conversion to a lipophilic amidinium salt. The biodegradable lipophilic modification of 2'-OMe-RNA resulted in a large increase in incorporation of such oligonucleotides into liposomes prepared by reversephase evaporation. Furthermore, association of these modified oligonucleotides with cultured TIB 73 cells was 100-fold higher than that seen with unmodified 2'-OMe-RNA in serum-free medium and about 10 to 30-fold higher in the presence of 10% calf serum. During incubation with cells, release of the internalized oligonucleotide from the thiocholesteryl moiety can be demonstrated.
摘要
通过在二氯甲烷 - 甲醇溶液中使3'-（吡啶二硫基）修饰的2'-O - 甲基寡核糖核苷酸（2'-OMe-RNA）与硫代胆固醇反应，胆固醇通过二硫键与2'-O - 甲基寡核糖核苷酸（2'-OMe-RNA）相连。这种连接反应通过一种新策略得以实现，即通过将高电荷寡核苷酸转化为亲脂性脒盐使其可溶于非水溶剂。2'-OMe-RNA的可生物降解亲脂性修饰导致此类寡核苷酸掺入反相蒸发制备的脂质体中的量大幅增加。此外，在无血清培养基中，这些修饰的寡核苷酸与培养的TIB 73细胞的结合比未修饰的2'-OMe-RNA高100倍，在含有10%小牛血清的情况下高约10至30倍。在与细胞孵育期间，可以证明内化的寡核苷酸从硫代胆固醇部分释放。
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