Linear consecutive hexaoxazoles as G4 ligands inducing chair-type anti-parallel topology of a telomeric G-quadruplex

Sasaki, Satoshi; Ma, Yue; Ishizuka, Takumi; Bao, Hong‐Liang; Hirokawa, Takatsugu; Xu, Yan; Tera, Masayuki

doi:10.1039/d0ra09413g

Cited by 7 publications

(4 citation statements)

References 69 publications

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“…19 F is not naturally present in the intracellular space; the 19 F-detected in-cell NMR spectra are free of spectral background. Xu et al showed that the 3,5-bis(trifluoromethyl)phenyl group ( Figure 4 A), referred to as 19 F-probe onwards, linked to 5’-terminus of DNA allows discrimination of G4 topologies using 19 F-detected in-cell NMR [ 37 , 70 ].…”

Section: Resultsmentioning

confidence: 99%

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

Krafčík

Ištvánková

Džatko

et al. 2021

IJMS

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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.

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Section: Resultsmentioning

confidence: 99%

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

Krafčík

Ištvánková

Džatko

et al. 2021

IJMS

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“…We have developed a series of polyoxazoles as G4 ligands, 43,44 and found that one of the linear-consecutive hexaoxazole series (6LCOs) selectively induces specific topology of telomeric G4. 45 The G4 ligand L2H2-2M2EA-6LCO (6LCO) was designed based upon the two-point recognition concept, i.e., targeting the G-quartet plane and the groove, and was synthesized as described in our previous report. 45 Here, we show that the enzymatic function of thrombin can be controlled by regulating the binding of thrombin with TBA through the induction of a specific TBA G4 topology with 6LCO (Fig.…”

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confidence: 99%

“…45 The G4 ligand L2H2-2M2EA-6LCO (6LCO) was designed based upon the two-point recognition concept, i.e., targeting the G-quartet plane and the groove, and was synthesized as described in our previous report. 45 Here, we show that the enzymatic function of thrombin can be controlled by regulating the binding of thrombin with TBA through the induction of a specific TBA G4 topology with 6LCO (Fig. 1C).…”

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confidence: 99%

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