Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Topoisomerase sites were mapped in the 5'-long terminal repeat of HIV-1 DNA by agarose and sequencing gel electrophoresis. Topoisomerase II sites were observed in the absence and presence of teniposide and amsacrine in the transcription initiation region and the TATA box, consistent with a possible role of topoisomerase II in transcription. The NF-kB and Sp1 regions were poorly cleaved. Topoisomerase I sites were relatively unfrequent even in the presence of camptothecin. They were absent in the core promoter and were concentrated in the TAR and the upstream region near the junction with the host DNA.
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PMID:DNA topoisomerases I & II cleavage sites in the type 1 human immunodeficiency virus (HIV-1) DNA promoter region. 781 Dec 42

The Human Immunodeficiency Virus (HIV) integrates into host cellular DNA as a double strand DNA molecule. Here a previously studied HIV isolate was examined for binding and cleavage by topoisomerase II in vitro within the 5' LTR region and human flanking DNA. A cluster of strong binding and cleavage sites in the human sequences was located approximately 850 bp upstream from the integration site. This region maps to a locus consisting of a complex repeating element, and alternating purine/pyrimidine sequences. Topoisomerase II binding and cleavage sites were also located within the HIV 5' LTR, in particular a site overlying the DNA sequence coding for TAR, another inverted repeat element in the DNA.
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PMID:A cluster of strong topoisomerase II cleavage sites is located near an integrated human immunodeficiency virus. 839 47

Quinolones represent an important class of broad-spectrum antibacterials, the main structural features of which are a 1,4 dihydro-4-oxo-quinolinyl moiety bearing an essential carboxyl group at position 3. Quinolones inhibit prokaryotic type II topoisomerases, namely DNA gyrase and, in a few cases, topoisomerase IV, through direct binding to the bacterial chromosome. Based on the hypothesis that these drugs could also bind to the viral nucleic acids or nucleoprotein-complexes, several quinolone derivatives were tested for their antiviral activity. Indeed, antibacterial fluoroquinolones were shown to be effective against vaccinia virus and papovaviruses; these preliminary results prompted the synthesis of modified quinolones to optimize antiviral action and improve selectivity index. The introduction of an aryl group at the piperazine moiety of the fluoroquinolone shifted the activity from antibacterial to antiviral, with a specific action against HIV. The antiviral activity seemed to be related to an inhibitory effect at the transcriptional level, and further evidence suggested a mechanism of action mediated by inhibition of Tat functions. Substitution of the fluorine at position 6 with an amine group to give aryl-piperazinyl-6-amino-quinolones improved the activity and selectivity against HIV-1: the most potent compound of this series was shown to inhibit virus replication through interference with Tat-TAR interaction. A comprehensive SAR investigation was performed based on additional chemical intervention to the quinolone template moiety, such as the introduction of nucleoside derivative functions. The information gained so far will be useful for future rational drug design aimed at developing new compounds with optimized antiviral activity.
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PMID:Antiviral properties of quinolone-based drugs. 1518 Apr 59