Studies on the hydrolytic stability of 2'-fluoroarabinonucleic acid (2'F-ANA)

Org Biomol Chem. 2009 May 7;7(9):1904-10. doi: 10.1039/b900443b. Epub 2009 Mar 19.


The stability of 2'-deoxy-2'-fluoroarabinonucleic acid (2'F-ANA) to hydrolysis under acidic and basic conditions was compared to that of DNA, RNA and 2'F-RNA. In enzyme-free simulated gastric fluid (pH approximately 1.2), 2'F-ANA was found to have dramatically increased stability (virtually no cleavage observed after 2 days) with respect to both DNA (t(1/2) approximately 2 min) and RNA (t(1/2) approximately 3 h (PO) or 3 days (PS)). These results were observed for both phosphodiester and phosphorothioate backbones and with multiple mixed-base sequences. Under basic conditions, 2'F-ANA also showed good stability. In 1 M NaOH at 65 degrees C, 2'F-ANA had a t(1/2) of approximately 20 h, while RNA was entirely degraded in a few minutes. Furthermore, the nuclease cleavage of phosphorothioate 2'F-ANA and DNA by snake venom phosphodiesterase was studied in detail. One diastereomer of the PS-2'F-ANA linkage was found to be much more vulnerable to enzymatic cleavage than the other, which is parallel to the properties observed for PS-DNA. Additional studies of 2'F-ANA-containing oligonucleotides are warranted based on the excellent stability properties described here.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2',3'-Cyclic-Nucleotide Phosphodiesterases / metabolism
  • Acids
  • Alkalies
  • Animals
  • Arabinonucleotides / chemistry*
  • Arabinonucleotides / metabolism
  • Base Sequence
  • Catalysis
  • Crotalus / metabolism
  • DNA / chemistry
  • DNA / metabolism
  • Hydrolysis
  • Molecular Structure
  • RNA / chemistry
  • RNA / metabolism
  • Stereoisomerism
  • Viper Venoms / enzymology


  • 2'-deoxy-2'-fluoro-beta-D-arabinonucleic acid
  • Acids
  • Alkalies
  • Arabinonucleotides
  • Viper Venoms
  • RNA
  • DNA
  • 2',3'-Cyclic-Nucleotide Phosphodiesterases