Towards Profiling of the G-Quadruplex Targeting Drugs in the
Living Human Cells Using NMR Spectroscopy

J 2021

Towards Profiling of the G-Quadruplex Targeting Drugs in the Living Human Cells Using NMR Spectroscopy

KRAFČÍK, Daniel; Eva IŠTVÁNKOVÁ; Šimon DŽATKO; Pavlína VÍŠKOVÁ; S. FOLDYNOVA-TRANTIRKOVA et. al.

Základní údaje

Originální název

Towards Profiling of the G-Quadruplex Targeting Drugs in the Living Human Cells Using NMR Spectroscopy

Autoři

KRAFČÍK, Daniel; Eva IŠTVÁNKOVÁ; Šimon DŽATKO; Pavlína VÍŠKOVÁ; S. FOLDYNOVA-TRANTIRKOVA a Lukáš TRANTÍREK

Vydání

International Journal of Molecular Sciences, Basel, Multidisciplinary Digital Publishing Institute, 2021, 1422-0067

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Kód RIV

RIV/00216224:14740/21:00120234

Organizační jednotka

Středoevropský technologický institut

DOI

https://doi.org/10.3390/ijms22116042

UT WoS

000660126000001

EID Scopus

2-s2.0-85107286658

Klíčová slova anglicky

in-cell NMR; G-quadruplex; ligand; drug; Bcl2; telomeric DNA; KRAS; BRACO19; PhenDC3; NMM

Štítky

143160, CF NMR, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 15. 10. 2024 14:36, Ing. Jana Kuchtová

Anotace

V originále

Recently, the H-1-detected in-cell NMR spectroscopy has emerged as a unique tool allowing the characterization of interactions between nucleic acid-based targets and drug-like molecules in living human cells. Here, we assess the application potential of H-1 and F-19-detected in-cell NMR spectroscopy to profile drugs/ligands targeting DNA G-quadruplexes, arguably the most studied class of anti-cancer drugs targeting nucleic acids. We show that the extension of the original in-cell NMR approach is not straightforward. The severe signal broadening and overlap of H-1 in-cell NMR spectra of polymorphic G-quadruplexes and their complexes complicate their quantitative interpretation. Nevertheless, the H-1 in-cell NMR can be used to identify drugs that, despite strong interaction in vitro, lose their ability to bind G-quadruplexes in the native environment. The in-cell NMR approach is adjusted to a recently developed 3,5-bis(trifluoromethyl)phenyl probe to monitor the intracellular interaction with ligands using F-19-detected in-cell NMR. The probe allows dissecting polymorphic mixture in terms of number and relative populations of individual G-quadruplex species, including ligand-bound and unbound forms in vitro and in cellulo. Despite the probe's discussed limitations, the F-19-detected in-cell NMR appears to be a promising strategy to profile G-quadruplex-ligand interactions in the complex environment of living cells.

Návaznosti

NV19-08-00450, projekt VaV

Název: Atomárně rozlišená NMR spektroskopie in vivo jako nástroj pro biologické testování terapeuticky významných cílů v genomové ne-kanonické DNA a jejich interakcí s léčivy ve fenotypově diverzifikovaných nádorových buňkách.

Investor: Ministerstvo zdravotnictví ČR, Atomically resolved in vivo NMR spectroscopy as a novel tool for biological testing of therapeutically important genomic non-canonical DNA targets and their interactions with drugs in phenotypically diversified cancer cells.

90127, velká výzkumná infrastruktura

Název: CIISB II

Citovat

KRAFČÍK, Daniel; Eva IŠTVÁNKOVÁ; Šimon DŽATKO; Pavlína VÍŠKOVÁ; S. FOLDYNOVA-TRANTIRKOVA a Lukáš TRANTÍREK. Towards Profiling of the G-Quadruplex Targeting Drugs in the Living Human Cells Using NMR Spectroscopy. International Journal of Molecular Sciences. Basel: Multidisciplinary Digital Publishing Institute, 2021, roč. 22, č. 11, s. 6042-6055. ISSN 1422-0067. Dostupné z: https://doi.org/10.3390/ijms22116042.

@article{1838631,
   author = {Krafčík, Daniel and Ištvánková, Eva and Džatko, Šimon and Víšková, Pavlína and FoldynovaandTrantirkova, S. and Trantírek, Lukáš},
   article_location = {Basel},
   article_number = {11},
   doi = {https://doi.org/10.3390/ijms22116042},
   keywords = {in-cell NMR; G-quadruplex; ligand; drug; Bcl2; telomeric DNA; KRAS; BRACO19; PhenDC3; NMM},
   language = {eng},
   issn = {1422-0067},
   journal = {International Journal of Molecular Sciences},
   title = {Towards Profiling of the G-Quadruplex Targeting Drugs in the Living Human Cells Using NMR Spectroscopy},
   url = {https://www.mdpi.com/1422-0067/22/11/6042},
   volume = {22},
   year = {2021}
}

TY  - JOUR
ID  - 1838631
AU  - Krafčík, Daniel - Ištvánková, Eva - Džatko, Šimon - Víšková, Pavlína - Foldynova-Trantirkova, S. - Trantírek, Lukáš
PY  - 2021
TI  - Towards Profiling of the G-Quadruplex Targeting Drugs in the Living Human Cells Using NMR Spectroscopy
JF  - International Journal of Molecular Sciences
VL  - 22
IS  - 11
SP  - 6042
EP  - 6042
PB  - Multidisciplinary Digital Publishing Institute
SN  - 14220067
KW  - in-cell NMR
KW  - G-quadruplex
KW  - ligand
KW  - drug
KW  - Bcl2
KW  - telomeric DNA
KW  - KRAS
KW  - BRACO19
KW  - PhenDC3
KW  - NMM
UR  - https://www.mdpi.com/1422-0067/22/11/6042
N2  - Recently, the H-1-detected in-cell NMR spectroscopy has emerged as a unique tool allowing the characterization of interactions between nucleic acid-based targets and drug-like molecules in living human cells. Here, we assess the application potential of H-1 and F-19-detected in-cell NMR spectroscopy to profile drugs/ligands targeting DNA G-quadruplexes, arguably the most studied class of anti-cancer drugs targeting nucleic acids. We show that the extension of the original in-cell NMR approach is not straightforward. The severe signal broadening and overlap of H-1 in-cell NMR spectra of polymorphic G-quadruplexes and their complexes complicate their quantitative interpretation. Nevertheless, the H-1 in-cell NMR can be used to identify drugs that, despite strong interaction in vitro, lose their ability to bind G-quadruplexes in the native environment. The in-cell NMR approach is adjusted to a recently developed 3,5-bis(trifluoromethyl)phenyl probe to monitor the intracellular interaction with ligands using F-19-detected in-cell NMR. The probe allows dissecting polymorphic mixture in terms of number and relative populations of individual G-quadruplex species, including ligand-bound and unbound forms in vitro and in cellulo. Despite the probe's discussed limitations, the F-19-detected in-cell NMR appears to be a promising strategy to profile G-quadruplex-ligand interactions in the complex environment of living cells.
ER  -

KRAFČÍK, Daniel; Eva IŠTVÁNKOVÁ; Šimon DŽATKO; Pavlína VÍŠKOVÁ; S. FOLDYNOVA-TRANTIRKOVA a Lukáš TRANTÍREK. Towards Profiling of the G-Quadruplex Targeting Drugs in the Living Human Cells Using NMR Spectroscopy. \textit{International Journal of Molecular Sciences}. Basel: Multidisciplinary Digital Publishing Institute, 2021, roč.~22, č.~11, s.~6042-6055. ISSN~1422-0067. Dostupné z: https://doi.org/10.3390/ijms22116042.

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