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Antitumor substitution-inert polynuclear platinum complexes stabilize G-quadruplex DNA and suppress G-quadruplex-mediated gene expression
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SYSNO ASEP 0554901 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Antitumor substitution-inert polynuclear platinum complexes stabilize G-quadruplex DNA and suppress G-quadruplex-mediated gene expression Author(s) Malina, Jaroslav (BFU-R) ORCID
Kostrhunová, Hana (BFU-R) RID, ORCID
Farrell, N. (US)
Brabec, Viktor (BFU-R) RID, ORCIDNumber of authors 4 Source Title Inorganic Chemistry Frontiers. - : Royal Society of Chemistry - ISSN 2052-1553
Roč. 8, č. 13 (2021), s. 3371-3381Number of pages 11 s. Publication form Print - P Language eng - English Country GB - United Kingdom Keywords myc g-quadruplex ; promoter region ; phosphate clamp ; metal-complexes ; nucleic-acids OECD category Organic chemistry R&D Projects GC20-14082J GA ČR - Czech Science Foundation (CSF) Method of publishing Limited access Institutional support BFU-R - RVO:68081707 UT WOS 000660065800001 EID SCOPUS 85109094177 DOI 10.1039/d1qi00488c Annotation DNA G-quadruplex (G4) structures formed in the telomeric and promoter regions represent attractive drug targets for anticancer therapy. Thus, much effort has been devoted to the development of a variety of G4-binding ligands, mostly based on rigid planar structures. Here, we investigated the efficacy of inherently flexible anticancer substitution-inert polynuclear platinum(s) complexes (SI-PPCs) to stabilize DNA G4s and terminate DNA polymerization on templates containing G4-forming sequences. Conventional DNA polymerase primer extension assay, fluorescence melting studies, fluorescence indicator displacement assay and circular dichroism spectroscopy revealed that SI-PPCs can stabilize DNA G4s and terminate DNA polymerization on templates containing G4-forming sequences although they lack structural properties of traditional G4 binders. Despite that the selectivity for G4 DNA over double-stranded DNA was somewhat lower than that observed for some traditional G4-binding ligands, it was notable that one of the investigated SI-PPCs, anticancer Triplatin NC, reduced the expression of G4-regulated genes c-myc and c-kit in human embryonic kidney cells. These results demonstrate that the overall biological activity of SI-PPCs can also involve interactions of SI-PPCs with different cellular targets acting as multi-target-directed compounds. Workplace Institute of Biophysics Contact Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Year of Publishing 2022 Electronic address https://pubs.rsc.org/en/content/articlelanding/2021/QI/D1QI00488C
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