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In-cell NMR of a DNA G-quadruplex and ligand

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A parallel d(TG4T)4 G-quadruplex remains NMR-visible and long-lived in Xenopus oocytes, but ligand 360A can hide the complex on the NMR timescale.

Source

G-quadruplex DNA and ligand interaction in living cells using NMR spectroscopy

Salgado GF, Cazenave C, Kerkour A, et al. · Chemical science · 2015

doi.org/10.1039/c4sc03853cRead the full paper ↗70 citationscc by

Study at a glance

Design
Animal / in-vitro — In-cell NMR of 15N/13C-labeled d(TG4T)4 microinjected into Xenopus oocytes ± 360A ligand
N
Oocyte in-cell NMR — no single reported oocyte analytic N in stored summary
Population
Living Xenopus laevis oocytes
Outcome
Intracellular G-quadruplex persistence and ligand-bound NMR visibility

Structured fields used in claim comparison tables when every cited study has a complete layer.

What they did

Authors micro-injected 15N/13C-labeled d(TG4T)4 into living Xenopus laevis oocytes and recorded 800 MHz SOFAST-HMQC imino spectra with and without the G-quadruplex ligand 360A, comparing in-cell and in vitro fingerprints.

What they found

The all-parallel G-quadruplex forms in cells and survives enzymatic attack for many hours. Ligand-bound oligonucleotide appears NMR-invisible in cells, implying extra binding partners or precipitation, so in vitro ligand studies may not transfer directly.

The limits

What it doesn't show

The study uses oocytes, not human tumor cells, and does not assign the cellular partners that silence the ligand complex.

Key terms

G-quadruplex
Stacked guanine quartets stabilized by Hoogsteen hydrogen bonds and cations such as K+.
Imino signature
Downfield 1H NMR peaks of guanine imino protons that report G-quadruplex fold.
SOFAST-HMQC
Fast 2D 1H–15N correlation experiment used here for in-cell imino detection.
360A
A G-quadruplex-binding ligand titrated against d(TG4T)4.
In-cell NMR
NMR of labeled molecules inside living cells rather than in dilute buffer.

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In-cell NMR here shows d(TG4T)4 is:

Common questions

Does the G-quadruplex fold in cells?

Yes—imino NMR shows the parallel d(TG4T)4 fold under physiological conditions.

What happens with ligand 360A in cells?

The complex can become NMR-invisible, unlike typical in vitro spectra.

What cells were used?

Living Xenopus laevis oocytes.

Why record at ~16 °C?

To limit cell damage while still seeing imino signals.

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