Exploring the binding of mitoxantrone to DNA using optical tweezers.

Abstract

Mitoxantrone (MTX) is a synthetic anti-cancer drug that displays intercalation binding mode with DNA. It has been widely studied using conventional methods, but not using single molecule techniques which can provide molecular level details of the interactions. Here we explored the binding of MTX with DNA using optical tweezers. Our optical tweezers set-up uses two counter propagating lasers to trap and manipulate a single DNA molecule that is stretched to measure the force response as a function of extension. The DNA stretching was repeated in the presence of various nano-molar concentrations of MTX at different pulling rates. Stretching at much slower pulling rates exhibited closer to binding equilibrium, indicating MTX is a slow binder with the time scale of seconds compared to classical intercalators which have microsecond binding kinetics. This will provide more detail about the binding mechanism of MTX that can be used to better understand the binding of MTX and also develop similar drug designs.