Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers
Abstract 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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-07-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12951-018-0381-y |
| _version_ | 1798034621337698304 |
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| author | Dennis Kreft Ying Wang Michael Rattay Katja Toensing Dario Anselmetti |
| author_facet | Dennis Kreft Ying Wang Michael Rattay Katja Toensing Dario Anselmetti |
| author_sort | Dennis Kreft |
| collection | DOAJ |
| description | Abstract 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 K a ≈ 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. |
| first_indexed | 2024-04-11T20:46:45Z |
| format | Article |
| id | doaj.art-ee44d48ab9c04ba0b348f4d8ec7273e2 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-11T20:46:45Z |
| publishDate | 2018-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-ee44d48ab9c04ba0b348f4d8ec7273e22022-12-22T04:04:00ZengBMCJournal of Nanobiotechnology1477-31552018-07-011611710.1186/s12951-018-0381-yBinding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezersDennis Kreft0Ying Wang1Michael Rattay2Katja Toensing3Dario Anselmetti4Experimental Biophysics and Applied Nanoscience, Physics Department, Bielefeld Institute for Nanoscience (BINAS), Bielefeld UniversityExperimental Biophysics and Applied Nanoscience, Physics Department, Bielefeld Institute for Nanoscience (BINAS), Bielefeld UniversityBaxter Oncology GmbHExperimental Biophysics and Applied Nanoscience, Physics Department, Bielefeld Institute for Nanoscience (BINAS), Bielefeld UniversityExperimental Biophysics and Applied Nanoscience, Physics Department, Bielefeld Institute for Nanoscience (BINAS), Bielefeld UniversityAbstract 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 K a ≈ 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.http://link.springer.com/article/10.1186/s12951-018-0381-yMitoxantroneDNAMagnetic tweezersIntercalatorGroove binder |
| spellingShingle | Dennis Kreft Ying Wang Michael Rattay Katja Toensing Dario Anselmetti Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers Journal of Nanobiotechnology Mitoxantrone DNA Magnetic tweezers Intercalator Groove binder |
| title | Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers |
| title_full | Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers |
| title_fullStr | Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers |
| title_full_unstemmed | Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers |
| title_short | Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers |
| title_sort | binding mechanism of anti cancer chemotherapeutic drug mitoxantrone to dna characterized by magnetic tweezers |
| topic | Mitoxantrone DNA Magnetic tweezers Intercalator Groove binder |
| url | http://link.springer.com/article/10.1186/s12951-018-0381-y |
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