Fe-II Metallohelices Stabilize DNA G-Quadruplexes and Downregulate the Expression of G-Quadruplex-Regulated Oncogenes
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F21%3A00553650" target="_blank" >RIV/68081707:_____/21:00553650 - isvavai.cz</a>
Result on the web
<a href="https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/chem.202101388" target="_blank" >https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/chem.202101388</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/chem.202101388" target="_blank" >10.1002/chem.202101388</a>
Alternative languages
Result language
angličtina
Original language name
Fe-II Metallohelices Stabilize DNA G-Quadruplexes and Downregulate the Expression of G-Quadruplex-Regulated Oncogenes
Original language description
DNA G-quadruplexes (G4s) have been identified within the promoter regions of many proto-oncogenes. Thus, G4s represent attractive targets for cancer therapy, and the design and development of new drugs as G4 binders is a very active field of medicinal chemistry. Here, molecular biophysics and biology methods were employed to investigate the interaction of chiral metallohelices with a series of four DNA G4s (hTelo, c-myc, c-kit1, c-kit2) that are formed by the human telomeric sequence (hTelo) and in the promoter regions of c-MYC and c-KIT proto-oncogenes. We show that the investigated water-compatible, optically pure metallohelices, which are made by self-assembly of simple nonpeptidic organic components around Fe-II ions and exhibit bioactivity emulating the natural systems, bind with high affinity to G4 DNA and much lower affinity to duplex DNA. Notably, both enantiomers of a metallohelix containing a m-xylenyl bridge (5 b) were found to effectively inhibit primer elongation catalyzed by Taq DNA polymerase by stabilizing G4 structures formed in the template strands containing c-myc and c-kit2 G4-forming sequences. Moreover, both enantiomers of 5 b downregulated the expression of c-MYC and c-KIT oncogenes in human embryonic kidney cells at mRNA and protein levels. As metallohelices also bind alternative nucleic acid structures, they hold promise as potential multitargeted drugs.
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
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Chemistry - A European Journal
ISSN
0947-6539
e-ISSN
1521-3765
Volume of the periodical
27
Issue of the periodical within the volume
45
Country of publishing house
DE - GERMANY
Number of pages
11
Pages from-to
11682-11692
UT code for WoS article
000667328900001
EID of the result in the Scopus database
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