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 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 a

SUBMITTER: Kreft D 

PROVIDER: S-EPMC6043947 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature