Issue 8, 2019

Imidazole-modified G-quadruplex DNA as metal-triggered peroxidase


Four imidazoles, serving as metalloprotein-inspired ligands for complexing a range of transition metal cations, were incorporated into tetramolecular G-quadruplex DNA structures. Modified quadruplexes were found to complex Cu(II), Ni(II), Zn(II) and Co(II) in a 1 : 1 ratio with unprecedented strong thermal stabilizations of up to ΔT1/2 = +51 °C. Furthermore, addition of Cu(II) was found to lead to extraordinarily fast G-quadruplex association rates with kon values being ∼100 times higher compared to unmodified G-quadruplexes. This is ascribed to a template effect of Cu(II), preorganizing the four single strands via coordination, followed by rapid formation of hydrogen-bonded G-quartets. Native electrospray ionization mass spectrometry (ESI), coupled with trapped ion-mobility spectrometry (timsTOF), supports the proposed 1 : 1 G-quadruplex-metal complexes and could further disclose their ability to bind the iron–porphyrin complex hemin in a 1 : 1 stoichiometry. DNA sequence design allowed us to equip this G-quadruplex-hemin complex, known to function as a horseradish peroxidase mimic, with a metal-dependent trigger. A competitive screen of transition metals revealed a high selectivity for Cu(II), even in mixtures of several divalent metal cations. Once formed, the Cu(II)-carrying DNAzyme was shown to be preserved in the presence of EDTA, attributed to its remarkable kinetic stability. Stimuli-responsive G-quadruplexes promise application in DNAzymes with switchable activity, adaptive sensors and dynamic DNA origami constructs.

Graphical abstract: Imidazole-modified G-quadruplex DNA as metal-triggered peroxidase

Supplementary files

Article information

Article type
Edge Article
11 Nov 2018
31 Dec 2018
First published
07 Jan 2019
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., 2019,10, 2513-2518

Imidazole-modified G-quadruplex DNA as metal-triggered peroxidase

Philip M. Punt and G. H. Clever, Chem. Sci., 2019, 10, 2513 DOI: 10.1039/C8SC05020A

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