|
ИСТИНА |
Войти в систему Регистрация |
ИСТИНА ЦЭМИ РАН |
||
Modulation of HIV-1 integrase activity by single-stranded oligonucleotides and their conjugates with eosinстатья
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 18 июля 2013 г.
- Авторы: Korolev Sergey, Knyazhanskaya Ekaterina, Anisenko Andrey, Tashlitskii Vadim, Zatsepin Timofei S., Gottikh Marina, Agapkina Julia
- Журнал: Nucleosides, Nucleotides and Nucleic Acids
- Том: 30
- Номер: 7-8
- Год издания: 2011
- Издательство: Marcel Dekker Inc.
- Местоположение издательства: United States
- Первая страница: 651
- Последняя страница: 666
- DOI: 10.1080/15257770.2011.592890
- Аннотация: Integration of the DNA copy of the genomic RNA into an infected cell genome is one of the key steps of the replication cycle of all retroviruses. It is catalyzed by the viral enzyme, integrase. We have shown that conjugates of short single-stranded oligonucleotides with eosin efficiently inhibit the catalytic activity of the HIV-1 integrase. In this article, we have found that the dependence of the integrase catalytic activity on the concentration of oligonucleotides has a bell-shaped pattern. The modulation of HIV-1 integrase activity correlated with the oligonucleotide length and was not associated with specific sequences. Moreover, a similar mode of the oligonucleotide action was found for integrase from the prototype foamy virus. This dual effect of the oligonucleotide and their conjugates with eosin might be explained by their binding with retroviral integrase in two different sites; the oligodeoxynucleotide binding in the first site results in integrase activation, whereas interactions with another one lead to inhibition of the enzyme activity. Eosin coupling to oligonucleotides did not change the mode of their action but enhanced their affinity to both binding sites. The affinity increase was found to be much more important for the site responsible for the integrase inhibition, thus explaining the high inhibitory potency of oligonucleotide-eosin conjugates.
- Добавил в систему: Зацепин Тимофей Сергеевич