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

Overview of attention for article published in Journal of Nanobiotechnology, July 2018
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Title
Binding mechanism of anti-cancer chemotherapeutic drug mitoxantrone to DNA characterized by magnetic tweezers
Published in
Journal of Nanobiotechnology, July 2018
DOI 10.1186/s12951-018-0381-y
Pubmed ID
Authors

Dennis Kreft, Ying Wang, Michael Rattay, Katja Toensing, Dario Anselmetti

Abstract

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. 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. 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. 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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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 40 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 40 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 20%
Student > Bachelor 5 13%
Student > Master 5 13%
Researcher 4 10%
Student > Doctoral Student 2 5%
Other 4 10%
Unknown 12 30%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 11 28%
Pharmacology, Toxicology and Pharmaceutical Science 4 10%
Physics and Astronomy 4 10%
Engineering 2 5%
Chemistry 2 5%
Other 3 8%
Unknown 14 35%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 July 2018.
All research outputs
#15,012,809
of 23,096,849 outputs
Outputs from Journal of Nanobiotechnology
#596
of 1,450 outputs
Outputs of similar age
#197,540
of 327,048 outputs
Outputs of similar age from Journal of Nanobiotechnology
#7
of 11 outputs
Altmetric has tracked 23,096,849 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,450 research outputs from this source. They receive a mean Attention Score of 3.5. This one has gotten more attention than average, scoring higher than 54% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 327,048 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 36th percentile – i.e., 36% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 11 others from the same source and published within six weeks on either side of this one. This one is in the 27th percentile – i.e., 27% of its contemporaries scored the same or lower than it.