Interaction of mithramycin with chromatin

Abstract

Mithramycin (MTR) is an anti-cancer antibiotic that blocks the macromolecular biosynthesis via reversible interaction with DNA template in the presence of bivalent metal ion such as Mg²⁺. In absence of DNA, mithramycin forms two types of complexes with Mg²⁺, complex I (with 1:1 stoichiometry in terms of MTR:Mg²⁺) and complex II (with 1:2 stoichiomelry in terms of MTR : Mg²⁺) . In an eukaryotic system, the drug would interact with chromatin, a protein - DNA complex. We have employed the spectroscopic techniques such as absorpt ion and fluorescence to study the interaction of MTR : Mg²⁺ complexes with rat liver chromatin. In this report, we have shown that the two types of ligands have different binding potentials with the same chromatin. This supports our proposition that complexes I and II, are different molecular species. We have also shown that the histone protein (s) reduce the binding potential and the number of available sites for both ligands.