Comparison between properties of 2'-O,4'-C-ethylene-bridged nucleic acid (ENA) phosphorothioate oligonucleotides and N3'-P5' thiophosphoramidate oligonucleotides.
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.
Horie
Makiko
M
Sankyo Co., Ltd., Lead Discovery Research Laboratories, Shinagawa-ku, Tokyo, Japan.
Morita
Koji
K
Kawakami
Junko
J
Ando
Osamu
O
Koizumi
Makoto
M
Tsutsumi
Shinya
S
D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D005030:Ethylenes / Q000737:chemistry*; D006358:Hot Temperature; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry*
D005030:Ethylenes; C479222:GRN163; D009841:Oligonucleotides; C036216:ethylene