Nuclease Resistance of Oligonucleotides Containing the Tricyclic Cytosine Analogues Phenoxazine and 9-(2-Aminoethoxy)-Phenoxazine (“G-clamp”) and Origins of Their Nuclease Resistance Properties

The tricyclic cytosine analogues phenoxazine and 9-(2-aminoethoxy)-phenoxazine (“G-clamp”) are known to significantly enhance the binding affinity of oligonucleotides to their complementary target DNA or RNA strands. To investigate their effect on the nuclease resistance, they were incorporated into...

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Bibliographic Details
Published in:Biochemistry (Easton) 2002-01, Vol.41 (4), p.1323-1327
Main Authors: Maier, Martin A, Leeds, Janet M, Balow, Guity, Springer, Robert H, Bharadwaj, Ramesh, Manoharan, Muthiah
Format: Article
Language:English
Subjects:
Animals
Cattle
Cytosine - analogs & derivatives
Hydrolysis
Oligonucleotides - chemistry
Oxazines - chemistry
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Summary:The tricyclic cytosine analogues phenoxazine and 9-(2-aminoethoxy)-phenoxazine (“G-clamp”) are known to significantly enhance the binding affinity of oligonucleotides to their complementary target DNA or RNA strands. To investigate their effect on the nuclease resistance, they were incorporated into model oligomers with a natural phosphodiester backbone, and enzymatic degradation was monitored in an in vitro assay with snake venom phosphodiesterase as the hydrolytic enzyme. In both cases, a single incorporation at the 3‘-terminus completely protected the oligonucleotides against 3‘-exonuclease attack. Further investigations indicate that the observed high nuclease resistance is not due to the lack of binding affinity to the enzyme's active site, since these modified oligonucleotides were able to inhibit degradation of a natural DNA fragment by bovine intestinal mucosal phosphodiesterase in a dose-dependent manner.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi011725y