Number of the records: 1
Towards Profiling of the G-Quadruplex Targeting Drugs in the Living Human Cells Using NMR Spectroscopy
- 1.
SYSNO ASEP 0555334 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Towards Profiling of the G-Quadruplex Targeting Drugs in the Living Human Cells Using NMR Spectroscopy Author(s) Krafčík, D. (CZ)
Istvankova, E. (CZ)
Dzatko, S. (CZ)
Viskova, P. (CZ)
Foldynová-Trantírková, Silvie (BFU-R) ORCID
Trantírek, L. (CZ)Number of authors 6 Article number 6042 Source Title International Journal of Molecular Sciences. - : MDPI
Roč. 22, č. 11 (2021)Number of pages 14 s. Publication form Online - E Language eng - English Country CH - Switzerland Keywords structures in-vitro ; human telomere ; nucleic-acids ; dna ; rna ; ligands OECD category Biochemistry and molecular biology R&D Projects EF15_003/0000477 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support BFU-R - RVO:68081707 UT WOS 000660126000001 EID SCOPUS 85107286658 DOI 10.3390/ijms22116042 Annotation 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. Workplace Institute of Biophysics Contact Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Year of Publishing 2022 Electronic address https://www.mdpi.com/1422-0067/22/11/6042
Number of the records: 1