Highly accurate synthesis of the fully 2'-fluoro-modified oligonucleotide by Therminator DNA polymerases.
Oligonucleotides composed of natural nucleotides are inapplicable for biotechnical and therapeutic use due to its instability under biological conditions. Therminator DNA polymerases, mutant DNA polymerases of thermophilic marine archaea, show that they can efficiently synthesize fully 2'-fluoro-modified (2'F-) oligonucleotides. Furthermore, the sequence analysis reveals that the oligonucleotide sequence is highly accurate, especially the fidelity of a 2'F-oligonucleotide synthesized by Therminator II is more accurate than that of natural RNA synthesized by conventional RNA polymerase. These finding would be helpful for the synthesis of chemically modified oligonucleotides, for the use of biotechnical or medical applications.
Innovative Drug Discovery Research Laboratories, Shionogi & Co., Ltd., 3-1-1, Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
Takeshi
T
Kasuya
Innovative Drug Discovery Research Laboratories, Shionogi & Co., Ltd., 3-1-1, Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
Shinichiro
S
Hori
Innovative Drug Discovery Research Laboratories, Shionogi & Co., Ltd., 3-1-1, Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
Hisanao
H
Hiramatsu
Innovative Drug Discovery Research Laboratories, Shionogi & Co., Ltd., 3-1-1, Futaba-cho, Toyonaka, Osaka 561-0825, Japan. Electronic address: toru.yanagimoto@shionogi.co.jp.
Toru
T
Yanagimoto
D001105:Archaea / Q000201:enzymology*; D001483:Base Sequence; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D054879:Halogenation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D012313:RNA / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
D009841:Oligonucleotides; D012313:RNA; D004259:DNA-Directed DNA Polymerase
2′-Fluoro-NTP; Biosynthesis; DNA polymerase; Fidelity; Oligonucleotide