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

Studies on the hydrolytic stability of 2?-fluoroarabinonucleic acid (2?F-ANA)
Studies on the hydrolytic stability of 2?-fluoroarabinonucleic acid (2?F-ANA)
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
1477-0520
1904
Watts, Jonathan K.
c4de85ee-aaa3-4e7d-99b3-147a4de4f01c
Katolik, Adam
c46df88f-db9d-4aeb-8cb7-49ae8a3a21f8
Viladoms, Júlia
264b5a9a-4d65-4246-981d-1f043eac5b05
Damha, Masad J.
31a9645e-2a72-4cc5-aa35-b82a16f1d535
Watts, Jonathan K.
c4de85ee-aaa3-4e7d-99b3-147a4de4f01c
Katolik, Adam
c46df88f-db9d-4aeb-8cb7-49ae8a3a21f8
Viladoms, Júlia
264b5a9a-4d65-4246-981d-1f043eac5b05
Damha, Masad J.
31a9645e-2a72-4cc5-aa35-b82a16f1d535

Watts, Jonathan K., Katolik, Adam, Viladoms, Júlia and Damha, Masad J. (2009) Studies on the hydrolytic stability of 2?-fluoroarabinonucleic acid (2?F-ANA). Organic & Biomolecular Chemistry, 7 (9), 1904. (doi:10.1039/B900443B). (PMID:19590787)

Record type: Article

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

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e-pub ahead of print date: 19 March 2009
Organisations: Chemistry, Organic Chemistry: SCF

Identifiers

Local EPrints ID: 342429
URI: http://eprints.soton.ac.uk/id/eprint/342429
ISSN: 1477-0520
PURE UUID: c635df6d-6f36-4659-9546-db5595fce89b

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Date deposited: 29 Aug 2012 11:39
Last modified: 14 Mar 2024 11:51

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Contributors

Author: Jonathan K. Watts
Author: Adam Katolik
Author: Júlia Viladoms
Author: Masad J. Damha

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