Dinuclear nickel(ii) supramolecular helicates down-regulate gene expression in human cells by stabilizing DNA G-quadruplexes formed in the promoter regions
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F22%3A00563243" target="_blank" >RIV/68081707:_____/22:00563243 - isvavai.cz</a>
Result on the web
<a href="https://pubs.rsc.org/en/content/articlelanding/2022/QI/D2QI01435A" target="_blank" >https://pubs.rsc.org/en/content/articlelanding/2022/QI/D2QI01435A</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1039/d2qi01435a" target="_blank" >10.1039/d2qi01435a</a>
Alternative languages
Result language
angličtina
Original language name
Dinuclear nickel(ii) supramolecular helicates down-regulate gene expression in human cells by stabilizing DNA G-quadruplexes formed in the promoter regions
Original language description
We investigated the interaction of the M- and P-enantiomers of the dinuclear nickel(ii) tetracationic supramolecular helicate ([Ni2L3](4+), L = C25H20N4) with a series of four DNA G-quadruplexes (G4s) (hTelo, c-myc, c-kit1, c-kit2) formed by the human telomeric sequence (hTelo) and in the promoter regions of c-MYC and c-KIT oncogenes. Utilizing a multi-platform approach based on biochemical and molecular biophysics methods to study these interactions, we show that [Ni2L3](4+) helicates preferably bind to G4s over duplex DNA and that their binding selectivities towards DNA G4 structures are comparable to those of renowned G4 binders. Additionally, primer extension studies on DNA templates containing G4-forming sequences proved that stabilization of hTelo and particularly c-myc G4s by the nickel(ii) helicates was sufficient to cause premature termination of DNA synthesis catalyzed by Taq DNA polymerase. We also confirmed that nickel helicates are taken up by human embryonic kidney (HEK 293) cells and enter the nucleus, where they bind to DNA. Results from qRT-PCR and western blotting demonstrated that [Ni2L3](4+) helicates downregulate c-MYC expression at mRNA and protein levels in HEK 293 cells in a dose-dependent manner.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10401 - Organic chemistry
Result continuities
Project
<a href="/en/project/GA20-00735S" target="_blank" >GA20-00735S: Metallo-supramolecular helicates as DNA condensing agents and carriers for DNA delivery</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Inorganic Chemistry Frontiers
ISSN
2052-1553
e-ISSN
2052-1553
Volume of the periodical
9
Issue of the periodical within the volume
21
Country of publishing house
GB - UNITED KINGDOM
Number of pages
10
Pages from-to
5597-5606
UT code for WoS article
000853772100001
EID of the result in the Scopus database
2-s2.0-85139428545