Issue 5, 2016

Small molecule regulated dynamic structural changes of human G-quadruplexes

Abstract

The changes in structure and dynamics of oncogenic (c-MYC) and telomeric (h-TELO) G-rich DNA sequences due to the binding of a novel carbazole derivative (BTC) are elucidated using single-molecule Förster resonance energy transfer (sm-FRET), fluorescence correlation spectroscopy (FCS) and NMR spectroscopy. In contrast to the previous reports on the binding of ligands to pre-folded G-quadruplexes, this work illustrates how ligand binding changes the conformational equilibria of both unstructured G-rich DNA sequences and K+-folded G-quadruplexes. The results demonstrate that K+ free c-MYC and h-TELO exist as unfolded and partially folded conformations. The binding of BTC shifts the equilibria of both investigated DNA sequences towards the folded G-quadruplex structure, increases the diffusion coefficients and induces faster end-to-end contact formation. BTC recognizes a minor conformation of the c-MYC quadruplex and the two-tetrad basket conformations of the h-TELO quadruplex.

Graphical abstract: Small molecule regulated dynamic structural changes of human G-quadruplexes

Supplementary files

Article information

Article type
Edge Article
Submitted
06 Jan 2016
Accepted
02 Feb 2016
First published
12 Feb 2016
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2016,7, 3279-3285

Small molecule regulated dynamic structural changes of human G-quadruplexes

M. Debnath, S. Ghosh, D. Panda, I. Bessi, H. Schwalbe, K. Bhattacharyya and J. Dash, Chem. Sci., 2016, 7, 3279 DOI: 10.1039/C6SC00057F

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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