Small Dumbbell Oligonucleotides Inhibitors of RNase H Activity of MOMULV Reverse Transcriptase
The small dumbbell oligonucleotides containing loops of phosphodiester (OL-1), two trimethylene, C3 moieties in each loop (OL-2) and phosphorothioate (OL-3) linkages were synthesized. Incubation of OL-1 and OL-2 with S-1 nuclease generated break down products whereas incubation of OL-3 did not resul...
Saved in:
| Main Author: | |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2011-01-01
|
| Series: | E-Journal of Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2011/584368 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | The small dumbbell oligonucleotides containing loops of phosphodiester (OL-1), two trimethylene, C3 moieties in each loop (OL-2) and phosphorothioate (OL-3) linkages were synthesized. Incubation of OL-1 and OL-2 with S-1 nuclease generated break down products whereas incubation of OL-3 did not result in significant cleavage. Their binding to moloney murine leukemia virus reverse transcriptase was evaluated by PAGE band mobility shift assays. The OL-3 bound more strongly to the reverse transcriptase than OL-1 and OL-2. The dissociation constants evaluated using PAGE band mobility shift assays were of the order of 10-7. Investigation of inhibition of RNase H activity of reverse transcriptase showed that the OL-3 is a better inhibitor of the retroviral RNase H activity than both OL-1 and OL-2. Thus OL-3 may be used as RNase H inhibitor. Our studies demonstrated that this particularly designed oligonucleotide (OL-3) displays an IC50 of 25 nM in its inhibition on the reverse transcriptase RNase H activity, a magnitude lower than that of first nucleotide reverse transcriptase of HIV-1, tenofovir, introduced by Gilead Science in the market. |
|---|---|
| ISSN: | 0973-4945 2090-9810 |