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 (703 Slovensko, domácí), Eva IŠTVÁNKOVÁ (203 Česká republika, domácí), Šimon DŽATKO (703 Slovensko, domácí), Pavlína VÍŠKOVÁ (203 Česká republika, domácí), S. FOLDYNOVA-TRANTIRKOVA a Lukáš TRANTÍREK (203 Česká republika, garant, domácí)

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

Impakt faktor

Impact factor: 6.208

Kód RIV

RIV/00216224:14740/21:00120234

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.3390/ijms22116042

UT WoS

000660126000001

Klíčová slova anglicky

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

Štítky

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://dx.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 = {http://dx.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://dx.doi.org/10.3390/ijms22116042.

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