QN-302 demonstrates opposing effects between i-motif and G-quadruplex DNA structures in the promoter of the S100P gene

Effrosyni Alexandrou; Dilek Guneri; Stephen Neidle; Zoë A. E. Waller

doi:10.1039/D3OB01464A

QN-302 demonstrates opposing effects between i-motif and G-quadruplex DNA structures in the promoter of the S100P gene†

Effrosyni Alexandrou,

^a Dilek Guneri,

^a Stephen Neidle

*^a and Zoë A. E. Waller

*^a

Author affiliations

* Corresponding authors

^a School of Pharmacy, University College London, 29-39 Brunswick Square, London, UK
E-mail: s.neidle@ucl.ac.uk, z.waller@ucl.ac.uk

Abstract

GC-rich sequences can fold into G-quadruplexes and i-motifs and are known to control gene expression in many organisms. The potent G-quadruplex experimental anticancer drug QN-302 down-regulates a number of cancer-related genes, in particular S100P. Here we show this ligand has strong opposing effects with i-motif DNA structures and is one of the most potent i-motif destabilising agents reported to date. QN-302 down-regulates the expression of numerous cancer-related genes by pan-quadruplex targeting. QN-302 exhibits exceptional combined synergistic effects compared to many other G-quadruplex and i-motif interacting compounds. This work further emphasises the importance of considering G-quadruplex and i-motif DNA structures as one dynamic system.

This article is part of the themed collection: Celebrating the scientific accomplishments of RSC Fellows

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DOI: https://doi.org/10.1039/D3OB01464A
Article type: Communication
Submitted: 12 Sep 2023
Accepted: 24 Oct 2023
First published: 06 Nov 2023
This article is Open Access

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Org. Biomol. Chem., 2024,22, 55-58

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QN-302 demonstrates opposing effects between i-motif and G-quadruplex DNA structures in the promoter of the S100P gene

E. Alexandrou, D. Guneri, S. Neidle and Z. A. E. Waller, Org. Biomol. Chem., 2024, 22, 55 DOI: 10.1039/D3OB01464A

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.

Organic & Biomolecular Chemistry

QN-302 demonstrates opposing effects between i-motif and G-quadruplex DNA structures in the promoter of the S100P gene†

Abstract

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QN-302 demonstrates opposing effects between i-motif and G-quadruplex DNA structures in the promoter of the S100P gene

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