Everything about Topoisomerase Inhibitor totally explained
Topoisomerase inhibitors are
chemotherapy agents designed to interfere with the action of
topoisomerase enzymes (topoisomerase I and II), which are
enzymes that control the changes in
DNA structure by
catalyzing the breaking and rejoining of the
phosphodiester backbone of DNA strands during the normal
cell cycle.
In recent years, topoisomerases have become popular targets for
cancer chemotherapy treatments. It is thought that topoisomerase inhibitors block the
ligation step of the cell cycle, generating single and double stranded breaks that harm the integrity of the genome. Introduction of these breaks subsequently lead to apoptosis and cell death.
Topoisomerase inhibitors are often divided according to which type of enzyme it inhibits.
Compounds that target Type II topoisomerase
These inhibitors are split into two main classes: topoisomerase poisons, which target the topoisomerase-DNA complex, and topoisomerase inhibitors, which disrupt catalytic turnover.
Topo II poisons
Examples of topoisomerase poisons include the following:
eukaryotic type II topoisomerase inhibitors (topo II):
amsacrine,
etoposide, etoposide phosphate,
teniposide and
doxorubicin. These drugs are anti-cancer therapies.
bacterial type II topoisomerase inhibitors (gyrase and topo IV):
fluoroquinolones. These are antibacterials and include such flouroquinolones as Ciprofloxin.
Some of these poisons encourage the forward cleavage reaction (fluoroquinolones), while other poisons prevent the re-ligation of DNA (etoposide and teniposide).
Interestingly, poisons of type IIA topoisomerases can target prokayrotic and eukaryotic enzymes preferencially, making them attractive drug candidates. Ciprofloxin targets prokaryotes in excess of a thousan fold more than it targets eukaryotic topo IIs. The mechanism for this specificity is unknown, but drug resistant mutants cluster in regions around the active site.
Topo II inhibitors
Examples of topoisomerase inhibitors include ICRF-193. These inhibitors target the N-terminal ATPase domain of topo II and prevent topo II from turning over. The structure of this compound bound to the ATPase domain was solved by Classen (Proceedings of the National Academy of Science, 2004) showing that the drug binds in a non-competitive manner and locks down the dimerization of the ATPase domain. This is consistent with biochemistry performed by Janet Lindsley's lab (reference needed).
Further Information
Get more info on 'Topoisomerase Inhibitor'.
|
External Link Exchanges
Do you know how hard it is to get a link from a large encyclopaedia? Well we're different and will prove it. To get a link from us just add the following HTML to your site on a relevant page:
<a href="http://topoisomerase_inhibitor.totallyexplained.com">Topoisomerase inhibitor Totally Explained</a>
Then simply click through this link from your web page. Our crawlers will verify your link, extract the title of your web page and instantly add a link back to it. If you like you can remove the words Totally Explained and embed the link in article text.
As long as your link remains in place, we'll keep our link to you right here. Please play fair - our crawlers are watching. Your site must be closely related to this one's topic. Any kind of spamming, dubious practises or removing the link will result in your link from us being dropped and, potentially, your whole site being banned. |
