Synthesis and properties of 2'-modified-4'-thioRNA.
As a part of our ongoing research projects, we envisioned the synthesis of 2'-modified-4'-thioRNA, such as 2'-fluoro-4'-thioRNA (2'-F-4'-thioRNA) and 2'-O-methyl-4'-thioRNA (2'-OMe-4'-thioRNA) to enhance the potential of 4'-thioRNA. Appropriately protected 2'-deoxy-2'-fluoro-4'-thiouridine (6), -cytidine (10), and - adenosine (18), substrates for the synthesis of novel modified RNAs were successfully synthesized. The fullymodified RNA consisting of 2'-deoxy-2'-fluoro-4'-thionucleosides was synthesised, and we examined its abilities of hybridization and stability against nucleases. It was found that 2'-F-4'-thioRNA shows high hybridization ability to complementary RNA. Furthermore, 2'-F-4'-thioRNA has strong resistance toward degradation in 50% human plasma.
Takahashi
Mayumi
M
Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan.
Minakawa
Noriaki
N
Matsuda
Akira
A
D000577:Amides / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D005461:Fluorine / Q000737:chemistry; D006801:Humans; D009693:Nucleic Acid Hybridization; D010756:Phosphoric Acids / Q000737:chemistry; D012313:RNA / Q000737:chemistry; D013872:Thionucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D013873:Thionucleotides / Q000097:blood / Q000138:chemical synthesis / Q000737:chemistry*
D000577:Amides; D010756:Phosphoric Acids; D013872:Thionucleosides; D013873:Thionucleotides; D005461:Fluorine; D012313:RNA; D004247:DNA; C011067:phosphoramidic acid