Interaction of mithramycin with DNA. Evidence that mithramycin binds to DNA as a dimer in a right-handed screw conformation.

The CD and fluorescence properties of mithramycin have been used to follow its complexation to cations such as Mg2+ and Zn2+ and the binding of these complexes to DNA. At low concentration (less than 2 microM) in aqueous solution, mithramycin is always in the dimeric state, the conformation of the dimer being either a right-handed screw when the dimer is neutral, or a left-handed screw when the dimer is negatively charged. In the deprotonated state the dimer can bind one cation forming a complex [M2+(Mit-)2] which has a right-handed screw conformation. The stability constants of the complex at 37 degrees C in 0.1 M KCl are 4 x 10(5) and 1 x 10(6) for Mg2+ and Zn2+, respectively. The complex in the right-handed screw conformation binds DNA. In this case the stability constants of the complex [M2+ (Mit-)2] increase and are 3.6 x 10(6) and 1.2 x 10(7) for Mg2+ and Zn2+, respectively.