Antitumor Drug Mitoxantrone Do Not Preclude Salt-driven B-Z Transition of Poly (dG- dC)

Armen T Karapetyan,Yurik S Babayan,Margarita A Torosyan

doi:10.13189/ijbb.2015.030401

Abstract

Despite of the existence in literature of large number of reports the binding modes of mitoxantrone (MTX) with DNA must be subject to refinement. Moreover there is no any report yet on interaction of MTX with Z-DNA. Here we present results of circular dichroism (CD) studies on MTX binding to salt driven left-handed conformation of poly (dG- dC). It was shown, that in contrast with classical intercalating ligands (ethidium bromide, acridine orange etc.) that bind with B-form DNA and obstacle B-Z transition at high concentrations of NaCl MTX interferes B-Z transition, but does not prevent the transitions process, thus suggest the semi intercalating (partial stacking) mode of MTX interaction with Z-form of DNA.

Highlights

Discovery of existence of unusual DNA conformations (Z-DNA, cruciform, bent DNA, oligopurine oligopyrimidine structures, etc.), in living cells and intense study of their interaction with biological active ligands made it possible to presume that alternative structures could have a functional role in vivo [1,2,3,4,7,8]
In order to answer the question ”Is the mechanism of semi intercalator MTX binding with Z-DNA like that of ethidium bromide (EtBr) and other classical intercalators ?” we investigate the interaction of MTX with driven by 3.1M NaCl Z-form of poly(dG-dC)[1]
Several in vitro and in vivo experiments revealed the existence of unusual conformation of DNA, including left-handed DNA (Z-DNA) cruciform, bent DNA, oligopurine-oligopyrimidine parallel structures [4,5,6,7,8,9,10,11]

Summary

Introduction

Small molecules including anticancer drugs and antibiotics (ligands) correlate their biological and therapeutic activities with the ability of interaction with existence in living cells of various DNA conformations (B, A, Z, cruciform, etc.) [1,2,3,4,5,6].Discovery of existence of unusual DNA conformations (Z-DNA, cruciform, bent DNA, oligopurine oligopyrimidine structures, etc.), in living cells and intense study of their interaction with biological active ligands made it possible to presume that alternative structures could have a functional role in vivo [1,2,3,4,7,8]. Small molecules including anticancer drugs and antibiotics (ligands) correlate their biological and therapeutic activities with the ability of interaction with existence in living cells of various DNA conformations (B, A, Z, cruciform, etc.) [1,2,3,4,5,6].

Results

Conclusion