Metal-triggered topology switching in bipyridine-modified DNA G-quadruplexes
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Gaining control over DNA G-quadruplex topology bears potential to modulate and study their interaction with other biomacromolecules such as proteins. To achieve this, we
introduced bipyridine ligands into short oligonucleotide strands derived from telomeric regions of humans and Tetrahymena as well as into an oncogenic promoter region capable of forming such G-quadruplexes. This modification makes it possible to dynamically access different G-quadruplex topologies through the formation of chelate complexes within the quadruplex loop regions using metals such as Cu2+, Ni2+, Zn2+, Co2+ and Cd2+. The metal coordinated systems show enhanced stability towards thermal denaturation as well as a solvation-related response in the presence of molecular crowding reagents. Furthermore, herein introduced G-quadruplexes modified with bipyridine-metal complexes stay folded in cellulo and therefore show potential for creating new oligonucleotide-based diagnostic agents and therapeutics. Metal-stabilized G-quadruplexes will be suited as robust probes for
finding new protein binders, inducers for cellular pathways or decoys to sequester transcription factors.
introduced bipyridine ligands into short oligonucleotide strands derived from telomeric regions of humans and Tetrahymena as well as into an oncogenic promoter region capable of forming such G-quadruplexes. This modification makes it possible to dynamically access different G-quadruplex topologies through the formation of chelate complexes within the quadruplex loop regions using metals such as Cu2+, Ni2+, Zn2+, Co2+ and Cd2+. The metal coordinated systems show enhanced stability towards thermal denaturation as well as a solvation-related response in the presence of molecular crowding reagents. Furthermore, herein introduced G-quadruplexes modified with bipyridine-metal complexes stay folded in cellulo and therefore show potential for creating new oligonucleotide-based diagnostic agents and therapeutics. Metal-stabilized G-quadruplexes will be suited as robust probes for
finding new protein binders, inducers for cellular pathways or decoys to sequester transcription factors.
Date Issued
2026-08-12
Date Acceptance
2026-06-30
Citation
Nucleic Acids Research (NAR), 2026, 54 (14)
ISSN
0305-1048
Publisher
Oxford University Press
Journal / Book Title
Nucleic Acids Research (NAR)
Volume
54
Issue
14
Copyright Statement
©The Author(s) 2026. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
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Publication Status
Published
Article Number
gkag738
Date Publish Online
2026-07-28