| KRAFČÍKOVÁ, Michaela, Šimon DŽATKO, C. CARON, A. GRANZHAN, Radovan FIALA, Tomáš LOJA, M.P. TEULADE-FICHOU, T. FESSL, R. HANSEL-HERTSCH, J.L. MERGNY, S. FOLDYNOVA-TRANTIRKOVA a Lukáš TRANTÍREK. Monitoring DNA-Ligand Interactions in Living Human Cells Using NMR Spectroscopy. Journal of the American Chemical Society. Washington: American Chemical Society, 2019, roč. 141, č. 34, s. 13281-13285. ISSN 0002-7863. Dostupné z: https://dx.doi.org/10.1021/jacs.9b03031. |
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@article{1576499,
author = {Krafčíková, Michaela and Džatko, Šimon and Caron, C. and Granzhan, A. and Fiala, Radovan and Loja, Tomáš and TeuladeandFichou, M.P. and Fessl, T. and HanselandHertsch, R. and Mergny, J.L. and FoldynovaandTrantirkova, S. and Trantírek, Lukáš},
article_location = {Washington},
article_number = {34},
doi = {http://dx.doi.org/10.1021/jacs.9b03031},
keywords = {MINOR-GROOVE; NUCLEIC-ACID; DRUG DESIGN; DISCOVERY; BINDERS},
language = {eng},
issn = {0002-7863},
journal = {Journal of the American Chemical Society},
title = {Monitoring DNA-Ligand Interactions in Living Human Cells Using NMR Spectroscopy},
url = {https://pubs.acs.org/doi/pdf/10.1021/jacs.9b03031},
volume = {141},
year = {2019}
}
TY - JOUR
ID - 1576499
AU - Krafčíková, Michaela - Džatko, Šimon - Caron, C. - Granzhan, A. - Fiala, Radovan - Loja, Tomáš - Teulade-Fichou, M.P. - Fessl, T. - Hansel-Hertsch, R. - Mergny, J.L. - Foldynova-Trantirkova, S. - Trantírek, Lukáš
PY - 2019
TI - Monitoring DNA-Ligand Interactions in Living Human Cells Using NMR Spectroscopy
JF - Journal of the American Chemical Society
VL - 141
IS - 34
SP - 13281-13285
EP - 13281-13285
PB - American Chemical Society
SN - 00027863
KW - MINOR-GROOVE
KW - NUCLEIC-ACID
KW - DRUG DESIGN
KW - DISCOVERY
KW - BINDERS
UR - https://pubs.acs.org/doi/pdf/10.1021/jacs.9b03031
L2 - https://pubs.acs.org/doi/pdf/10.1021/jacs.9b03031
N2 - Studies on DNA-ligand interactions in the cellular environment are problematic due to the lack of suitable biophysical tools. To address this need, we developed an in-cell NMR-based approach for monitoring DNA-ligand interactions inside the nuclei of living human cells. Our method relies on the acquisition of NMR data from cells electroporated with preformed DNA-ligand complexes. The impact of the intracellular environment on the integrity of the complexes is assessed based on in-cell NMR signals from unbound and ligand-bound forms of a given DNA target. This technique was tested on complexes of two model DNA fragments and four ligands, namely, a representative DNA minor-groove binder (netropsin) and ligands binding DNA base-pairing defects (naphthalenophanes). In the latter case, we demonstrate that two of the three in vitro-validated ligands retain their ability to form stable interactions with their model target DNA in cellulo, whereas the third one loses this ability due to off-target interactions with genomic DNA and cellular metabolites. Collectively, our data suggest that direct evaluation of the behavior of drug-like molecules in the intracellular environment provides important insights into the development of DNA-binding ligands with desirable biological activity and minimal side effects resulting from off-target binding.
ER -
KRAFČÍKOVÁ, Michaela, Šimon DŽATKO, C. CARON, A. GRANZHAN, Radovan FIALA, Tomáš LOJA, M.P. TEULADE-FICHOU, T. FESSL, R. HANSEL-HERTSCH, J.L. MERGNY, S. FOLDYNOVA-TRANTIRKOVA a Lukáš TRANTÍREK. Monitoring DNA-Ligand Interactions in Living Human Cells Using NMR Spectroscopy. \textit{Journal of the American Chemical Society}. Washington: American Chemical Society, 2019, roč.~141, č.~34, s.~13281-13285. ISSN~0002-7863. Dostupné z: https://dx.doi.org/10.1021/jacs.9b03031.
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