Type of Publication: | Journal article |
URI (citable link): | http://nbn-resolving.de/urn:nbn:de:bsz:352-156235 |
Author: | Yamazaki, Satoko; Tan, Lu; Mayer, Günter; Hartig, Jörg; Song, Jin-Na; Reuter, Sandra; Restle, Tobias; Laufer, Sandra D.; Grohmann, Dina; Kräusslich, Hans-Georg; Bajorath, Jürgen; Famulok, Michael |
Year of publication: | 2007 |
Published in: | Chemistry & Biology ; 14 (2007), 7. - pp. 804-812. - ISSN 1074-5521 |
Pubmed ID: | 17656317 |
DOI (citable link): | https://dx.doi.org/10.1016/j.chembiol.2007.06.003 |
Summary: |
Aptamers targeting reverse transcriptase (RT) from HIV-1 inhibit viral replication in vitro, presumably by competing with binding of the primer/template complex. This site is not targeted by the currently available small-molecule anti-HIV-1 RT inhibitors. We have identified SY-3E4, a small-molecule inhibitor of HIV-1 RT, by applying a screening assay that utilizes a reporter-ribozyme regulated by the anti-HIV-1 RT aptamer. SY-3E4 displaces the aptamer from the protein, selectively inhibits DNA-dependent, but not RNA-dependent, polymerase activity, and inhibits the replication of both the wild-type virus and a multidrug-resistant strain. Analysis of available structural data of HIV-1 and HIV-2 RTs rationalizes many of the observed characteristics of the inhibitory profiles of SY-3E4 and the aptamer and suggests a previously not considered region in these RTs as a target for antiviral therapy. Our study reveals unexplored ways for rapidly identifying alternative small-molecule target sites in proteins and illustrates strategies for overcoming resistance-conferring mutations with small molecules.
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Subject (DDC): | 540 Chemistry |
Keywords: | Chembiology, microbiolgoy |
Link to License: | In Copyright |
Bibliography of Konstanz: | Yes |
YAMAZAKI, Satoko, Lu TAN, Günter MAYER, Jörg HARTIG, Jin-Na SONG, Sandra REUTER, Tobias RESTLE, Sandra D. LAUFER, Dina GROHMANN, Hans-Georg KRÄUSSLICH, Jürgen BAJORATH, Michael FAMULOK, 2007. Aptamer displacement identifies alternative small molecule target sites that escape viral resistance. In: Chemistry & Biology. 14(7), pp. 804-812. ISSN 1074-5521. Available under: doi: 10.1016/j.chembiol.2007.06.003
@article{Yamazaki2007-07Aptam-15623, title={Aptamer displacement identifies alternative small molecule target sites that escape viral resistance}, year={2007}, doi={10.1016/j.chembiol.2007.06.003}, number={7}, volume={14}, issn={1074-5521}, journal={Chemistry & Biology}, pages={804--812}, author={Yamazaki, Satoko and Tan, Lu and Mayer, Günter and Hartig, Jörg and Song, Jin-Na and Reuter, Sandra and Restle, Tobias and Laufer, Sandra D. and Grohmann, Dina and Kräusslich, Hans-Georg and Bajorath, Jürgen and Famulok, Michael} }
Yamazaki_156235.pdf | 1674 |