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...
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | E-Journal of Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2011/584368 |
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| author | Ajay Kumar |
| author_facet | Ajay Kumar |
| author_sort | Ajay Kumar |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e5662d1421ad4cb19f82cf22bada179d |
| institution | OA Journals |
| issn | 0973-4945 2090-9810 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | E-Journal of Chemistry |
| spelling | doaj-art-e5662d1421ad4cb19f82cf22bada179d2025-08-20T02:21:19ZengWileyE-Journal of Chemistry0973-49452090-98102011-01-018262963410.1155/2011/584368Small Dumbbell Oligonucleotides Inhibitors of RNase H Activity of MOMULV Reverse TranscriptaseAjay Kumar0Apeejay Stya University, Palwal Sohna Road, Gurgaon, Haryana, IndiaThe 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.http://dx.doi.org/10.1155/2011/584368 |
| spellingShingle | Ajay Kumar Small Dumbbell Oligonucleotides Inhibitors of RNase H Activity of MOMULV Reverse Transcriptase E-Journal of Chemistry |
| title | Small Dumbbell Oligonucleotides Inhibitors of RNase H Activity of MOMULV Reverse Transcriptase |
| title_full | Small Dumbbell Oligonucleotides Inhibitors of RNase H Activity of MOMULV Reverse Transcriptase |
| title_fullStr | Small Dumbbell Oligonucleotides Inhibitors of RNase H Activity of MOMULV Reverse Transcriptase |
| title_full_unstemmed | Small Dumbbell Oligonucleotides Inhibitors of RNase H Activity of MOMULV Reverse Transcriptase |
| title_short | Small Dumbbell Oligonucleotides Inhibitors of RNase H Activity of MOMULV Reverse Transcriptase |
| title_sort | small dumbbell oligonucleotides inhibitors of rnase h activity of momulv reverse transcriptase |
| url | http://dx.doi.org/10.1155/2011/584368 |
| work_keys_str_mv | AT ajaykumar smalldumbbelloligonucleotidesinhibitorsofrnasehactivityofmomulvreversetranscriptase |