2'-O,4'-C-ethylene-bridged nucleic acids (ENA) with nuclease-resistance and high affinity for RNA.
Novel nucleosides, 2'-O,4'-C-ethylene nucleosides and their corresponding phosphoramidites, were synthesized as building blocks for antisense oligonucleotides. The 2'-O,4'-C-ethylene linkage of these nucleosides, as well as the linkage of 2'-O,4'-C-methylene nucleosides which are known as bridged nucleic acids (BNA) or locked nucleic acids (LNA), restricts the sugar puckering to the N-conformation. The ethylene-bridged nucleic acids (ENA) showed a high binding affinity for the complementary RNA strand (delta Tm = degrees C/modification) and were approximately 400 and 80 times more nuclease-resistant than natural DNA and BNA/LNA, respectively. These results indicate that ENA have better antisense activity than BNA/LNA.
Morita
K
K
Exploratory Chemistry Research Laboratories, Sankyo Co., Ltd., Tokyo 140-8710, Japan.
Hasegawa
C
C
Kaneko
M
M
Tsutsumi
S
S
Sone
J
J
Ishikawa
T
T
Imanishi
T
T
Koizumi
M
M
D001483:Base Sequence; D004720:Endonucleases / Q000378:metabolism; D005030:Ethylenes / Q000737:chemistry*; D005092:Exonucleases / Q000378:metabolism; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000737:chemistry; D012313:RNA / Q000737:chemistry*; D012260:Ribonucleases / Q000378:metabolism
D005030:Ethylenes; D009705:Nucleosides; D016376:Oligonucleotides, Antisense; D009943:Organophosphorus Compounds; C434331:phosphoramidite; D012313:RNA; D004720:Endonucleases; D005092:Exonucleases; D012260:Ribonucleases