31394899 OR Monitoring DNA-Ligand Interactions in Living Human Cells Using NMR Spectroscopy
Dotaz
Zobrazit nápovědu
Recently, the 1H-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 1H and 19F-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 1H in-cell NMR spectra of polymorphic G-quadruplexes and their complexes complicate their quantitative interpretation. Nevertheless, the 1H 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 19F-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 19F-detected in-cell NMR appears to be a promising strategy to profile G-quadruplex-ligand interactions in the complex environment of living cells.
- MeSH
- DNA chemie účinky léků MeSH
- G-kvadruplexy účinky léků MeSH
- konformace nukleové kyseliny účinky léků MeSH
- léčivé přípravky chemie MeSH
- lidé MeSH
- ligandy MeSH
- magnetická rezonanční spektroskopie MeSH
- molekulární modely MeSH
- protony MeSH
- vazebná místa účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
... A. keiderling -- Raman and NMR Spectroscopy of the Elastin Like Polypentapeptides 31 viiTable of Contents ... ... Dines -- Monitoring Selective Substitutions of Amino Acids in Helical Peptides by Raman 33 -- Spectroscopy ... ... 69 -- Hemoglobin by FTIR Spectroscopy -- J. /■ Al-Mustafa Malkawi -- Interaction of c-Myb(R2R3) Fragment ... ... Belinsky -- Interaction of a New Antiviral and Antitumor Photosensitizer Hypericin with Human -- Serum ... ... Simon -- Fluorescence Study of Interactions between Aluminium Octacarboxyphtalocyanine and Human Serum ...
2 sv. (150 s., s. 151-274) : il., tab. ; 25 cm
