Monitoring DNA-Ligand Interactions in Living Human Cells Using NMR Spectroscopy

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F19%3A00518341" target="_blank" >RIV/68081707:_____/19:00518341 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14740/19:00107756 RIV/60076658:12310/19:43899573

Result on the web

<a href="https://pubs.acs.org/doi/pdf/10.1021/jacs.9b03031" target="_blank" >https://pubs.acs.org/doi/pdf/10.1021/jacs.9b03031</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/jacs.9b03031" target="_blank" >10.1021/jacs.9b03031</a>

Result language

angličtina

Original language name

Monitoring DNA-Ligand Interactions in Living Human Cells Using NMR Spectroscopy

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10406 - Analytical chemistry

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of the American Chemical Society

ISSN

0002-7863

e-ISSN

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Volume of the periodical

141

Issue of the periodical within the volume

34

Country of publishing house

US - UNITED STATES

Number of pages

5

Pages from-to

13281-13285

UT code for WoS article

000484082700001

EID of the result in the Scopus database

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