Detailed Information on Publication Record
2019
Monitoring DNA-Ligand Interactions in Living Human Cells Using NMR Spectroscopy
KRAFČÍKOVÁ, Michaela, Šimon DŽATKO, C. CARON, A. GRANZHAN, Radovan FIALA et. al.Basic information
Original name
Monitoring DNA-Ligand Interactions in Living Human Cells Using NMR Spectroscopy
Authors
KRAFČÍKOVÁ, Michaela (703 Slovakia, belonging to the institution), Šimon DŽATKO (703 Slovakia, belonging to the institution), C. CARON (250 France), A. GRANZHAN (250 France), Radovan FIALA (203 Czech Republic, belonging to the institution), Tomáš LOJA (703 Slovakia, belonging to the institution), M.P. TEULADE-FICHOU (250 France), T. FESSL (203 Czech Republic), R. HANSEL-HERTSCH (826 United Kingdom of Great Britain and Northern Ireland), J.L. MERGNY (250 France), S. FOLDYNOVA-TRANTIRKOVA (203 Czech Republic) and Lukáš TRANTÍREK (203 Czech Republic, guarantor, belonging to the institution)
Edition
Journal of the American Chemical Society, Washington, American Chemical Society, 2019, 0002-7863
Other information
Language
English
Type of outcome
Článek v odborném periodiku
Field of Study
10400 1.4 Chemical sciences
Country of publisher
United States of America
Confidentiality degree
není předmětem státního či obchodního tajemství
References:
Impact factor
Impact factor: 14.612
RIV identification code
RIV/00216224:14740/19:00107756
Organization unit
Central European Institute of Technology
UT WoS
000484082700001
Keywords in English
MINOR-GROOVE; NUCLEIC-ACID; DRUG DESIGN; DISCOVERY; BINDERS
Tags
International impact, Reviewed
Změněno: 30/10/2024 14:10, Ing. Martina Blahová
Abstract
V originále
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.
Links
| GA16-10504S, research and development project |
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| GX19-26041X, research and development project |
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| LM2015064, research and development project |
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| LQ1601, research and development project |
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| MUNI/E/0771/2018, interní kód MU |
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| 653706, interní kód MU |
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| 90043, large research infrastructures |
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| 90062, large research infrastructures |
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