Horie Makiko, Morita Koji, Kawakami Junko, Ando Osamu, Koizumi Makoto, Tsutsumi Shinya
Sankyo Co., Ltd., Lead Discovery Research Laboratories, Shinagawa-ku, Tokyo, Japan.
Nucleosides Nucleotides Nucleic Acids. 2006 Mar;25(3):231-42. doi: 10.1080/15257770500446881.
Synthesis and properties of an oligonucleotide uniformly modified with 2'-O,4-C-ethylene-bridged nucleic acid (ENA) units were compared with those of GRN163, which is modified with N3'-P5' thiophosphoramidates, with the sequence targeting human telomerase RNA subunit. Although an ENA phosphorothioate oligonucleotide, ENA-13, could be synthesized using ENA phosphoramidites on a 100-mg scale, synthesis of GRN163 was very hard even on a 1-micomol scale. In view of both stability of the duplex formation with complementary RNA and the efficiency of cellular uptake by endocytosis, ENA-13 was superior to GRN163. These findings suggest that ENA-13 has useful properties for antisense therapeutic application.
将用2'-O,4-C-乙烯桥连核酸（ENA）单元均匀修饰的寡核苷酸的合成及性质，与用N3'-P5'硫代磷酸酯修饰的GRN163（其序列靶向人端粒酶RNA亚基）的合成及性质进行了比较。尽管可以使用100毫克规模的ENA亚磷酰胺合成ENA硫代磷酸酯寡核苷酸ENA-13，但即使在1微摩尔规模下，GRN163的合成也非常困难。鉴于与互补RNA形成双链体的稳定性以及通过内吞作用进行细胞摄取的效率，ENA-13优于GRN163。这些发现表明ENA-13在反义治疗应用中具有有用的性质。
