Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers

Kreft D, Wang Y, Rattay M, Tönsing K, Anselmetti D (2018)
Journal of Nanobiotechnology 16: 56.

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Abstract / Bemerkung
Background Chemotherapeutic agents (anti-cancer drugs) are small cytostatic or cytotoxic molecules that often bind to double-stranded DNA (dsDNA) resulting in modifications of their structural and nanomechanical properties and thus interfering with the cell proliferation process. Methods We investigated the anthraquinone compound mitoxantrone that is used for treating certain cancer types like leukemia and lymphoma with magnetic tweezers as a single molecule nanosensor. In order to study the association of mitoxantrone with dsDNA, we conducted force-extension and mechanical overwinding experiments with a sensitivity of 10−14 N. Results Using this method, we were able to estimate an equilibrium constant of association Ka ≈ 1 × 105 M−1 as well as a binding site size of n ≈ 2.5 base pairs for mitoxantrone. An unwinding angle of mitoxantrone-intercalation of ϑ ≈ 16° was determined. Conclusion Moreover, we observed a complex concentration-dependent bimodal binding behavior, where mitoxantrone associates to dsDNA as an intercalator and groove binder simultaneously at low concentrations and as a mere intercalator at high concentrations.
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Zeitschriftentitel
Journal of Nanobiotechnology
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16
Art.-Nr.
56
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Article Processing Charge funded by the Deutsche Forschungsgemeinschaft and the Open Access Publication Fund of Bielefeld University.
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Kreft D, Wang Y, Rattay M, Tönsing K, Anselmetti D. Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers. Journal of Nanobiotechnology. 2018;16: 56.
Kreft, D., Wang, Y., Rattay, M., Tönsing, K., & Anselmetti, D. (2018). Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers. Journal of Nanobiotechnology, 16, 56. doi:10.1186/s12951-018-0381-y
Kreft, D., Wang, Y., Rattay, M., Tönsing, K., and Anselmetti, D. (2018). Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers. Journal of Nanobiotechnology 16:56.
Kreft, D., et al., 2018. Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers. Journal of Nanobiotechnology, 16: 56.
D. Kreft, et al., “Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers”, Journal of Nanobiotechnology, vol. 16, 2018, : 56.
Kreft, D., Wang, Y., Rattay, M., Tönsing, K., Anselmetti, D.: Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers. Journal of Nanobiotechnology. 16, : 56 (2018).
Kreft, Dennis, Wang, Ying, Rattay, Michael, Tönsing, Katja, and Anselmetti, Dario. “Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers”. Journal of Nanobiotechnology 16 (2018): 56.
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2018-08-02T11:39:27Z

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Correction to: Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers.
Kreft D, Wang Y, Rattay M, Toensing K, Anselmetti D., J Nanobiotechnology 17(1), 2019
PMID: 30736797

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