AI Article Synopsis
- The tricyclic cytosine analogues phenoxazine and "G-clamp" enhance the binding of oligonucleotides to their target DNA/RNA.
- Researchers tested their nuclease resistance by incorporating them into oligomers and monitoring degradation using snake venom phosphodiesterase.
- The results showed that a single modification at the 3’-end fully protected the oligonucleotides from degradation, indicating high nuclease resistance.
Article Abstract
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.
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| http://dx.doi.org/10.1021/bi011725y | DOI Listing |
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