title: Studies on the hydrolytic stability of 2'-fluoroarabinonucleic acid (2'F-ANA).
abstract: 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.
authors: Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, QC, Canada H3A 2K6.
authors: Jonathan K
authors: JK
authors: Watts
authors: Adam
authors: A
authors: Katolik
authors: Júlia
authors: J
authors: Viladoms
authors: Masad J
authors: MJ
authors: Damha
mesh_terms: D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000143:Acids; D000468:Alkalies; D000818:Animals; D001088:Arabinonucleotides / Q000737:chemistry* / Q000378:metabolism; D001483:Base Sequence; D002384:Catalysis; D017839:Crotalus / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D006868:Hydrolysis; D015394:Molecular Structure; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism; D014757:Viper Venoms / Q000201:enzymology
chemical_list: C507672:2'-deoxy-2'-fluoro-beta-D-arabinonucleic acid; D000143:Acids; D000468:Alkalies; D001088:Arabinonucleotides; D014757:Viper Venoms; D012313:RNA; D004247:DNA; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases