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 ∼1.2), 2′F-ANA was found to have dramatically increased stability (virtually no cleavage observed after 2 days) with respect to both DNA (t1/2∼ 2 min) and RNA (t1/2∼ 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 °C, 2′F-ANA had a t1/2 of ∼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.
