期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 60, 期 6, 页码 2169-2192出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.6b00966
关键词
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资金
- Associazione Italiana per la Ricerca sul Cancro, Milan, Italy [IG 15886]
- University of Bologna (FARB project Modulation of Protein DNA Interaction with Small Molecules: Novel Opportunities for Drug Design)
DNA topoisomerases constitute a large family of enzymes that are essential for all domains of life. Although they share general reaction chemistry and the capacity to govern DNA topology and resolve strand entanglements during fundamental molecular processes, they are characterized by differences in their structural organization, modes of enzymatic catalysis, and biological functions. Moreover, hundreds of compounds interfere with bacterial and/or eukaryotic enzymes, some of which are effective drugs for the treatment of infectious diseases and cancers. Research over the past decade has focused on the biological functions of DNA topoisomerases, and several findings have revealed unexpected roles of type I DNA topoisomerases, a subclass of these enzymes, in regulating gene expression and DNA and chromatin conformations. These new findings highlight that type I topoisomerases are still interesting targets for drug discovery for the treatment of several human diseases, including multidrug-resistant infections and genetic disorders.
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