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DNA binding by the antimalarial compound artemisinin.

Sladjana Slavkovic¹, Aron A Shoara¹, Zachary R Churcher¹

¹Department of Chemistry and Centre for Research on Biomolecular Interactions, York University, 4700 Keele St., Toronto, ON, M3J 1P3, Canada.

Scientific Reports

|January 8, 2022

Summary

Artemisinin (ART), an antimalarial drug, binds to DNA structures, specifically at three-way junctions. This DNA binding, driven by entropy and enthalpy, can be detected using aptamer-based biosensors.

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Toxicological Assays for Testing Effects of an Epigenetic Drug on Development, Fecundity and Survivorship of Malaria Mosquitoes

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Published on: January 16, 2015

Area of Science:

Biochemistry
Molecular Biology
Medicinal Chemistry

Background:

Artemisinin (ART) is a crucial antimalarial compound, typically functioning by interacting with heme and proteins.
The precise molecular mechanisms underlying ART's antimalarial activity, particularly potential interactions beyond heme and proteins, remain an area of investigation.

Purpose of the Study:

To investigate the potential for Artemisinin (ART) to bind with DNA molecules.
To characterize the biophysical interactions between ART and DNA using various techniques.
To explore the potential application of ART-DNA interactions in biosensing.

Main Methods:

Isothermal titration calorimetry (ITC) to determine binding thermodynamics.
Native mass spectrometry (MS) to confirm complex formation.
Nuclear magnetic resonance (NMR) spectroscopy to identify binding sites and structural changes.
Photochrome aptamer switch assay for biosensing applications.

Main Results:

Demonstrated that ART binds to DNA structures, including three-way junctions and duplex DNA.
ITC revealed ART-DNA binding is entropically and enthalpically driven.
Native MS confirmed the formation of a non-covalent ART-DNA complex.
NMR identified ART binding at the three-way junction of a cocaine-binding aptamer, inducing structural changes.

Conclusions:

This study provides the first evidence of Artemisinin (ART) binding to DNA.
ART-DNA interactions are thermodynamically favorable and involve specific binding sites.
The observed structure-switching of aptamers upon ART binding enables the development of novel ART biosensors.
Further research is warranted to elucidate the role of DNA binding in ART's antimalarial efficacy.