2. Academic Validation
  3. Highly accurate synthesis of the fully 2'-fluoro-modified oligonucleotide by Therminator DNA polymerases

Highly accurate synthesis of the fully 2'-fluoro-modified oligonucleotide by Therminator DNA polymerases

  • Bioorg Med Chem Lett. 2014 May 1;24(9):2134-6. doi: 10.1016/j.bmcl.2014.03.035.
Takeshi Kasuya 1,  Shinichiro Hori 1,  Hisanao Hiramatsu 1,  Toru Yanagimoto 2
Affiliations

Affiliations

  • 1 Innovative Drug Discovery Research Laboratories, Shionogi & Co., Ltd., 3-1-1, Futaba-cho, Toyonaka, Osaka 561-0825, Japan.
  • 2 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.
PMID: 24703229 DOI: 10.1016/j.bmcl.2014.03.035
Abstract

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.

Keywords

2′-Fluoro-NTP; Biosynthesis; DNA polymerase; Fidelity; Oligonucleotide.

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