ROLE OF MG++ IN THE MITHRAMYCIN-DNA INTERACTION - EVIDENCE FOR 2 TYPES OF MITHRAMYCIN-MG++ COMPLEX

Mithramycin (MTR, structure shown in Figure 1) [and the related compound Chromomycin A3 (CHRA3)] are antitumor antibiotics which inhibit DNA dependent RNA polymerase activity via reversible interaction with DNA only in the presence of divalent metal ion such as Mg++. In order to understand the role of Mg++ in MTR-DNA interaction, absorbance and CD spectroscopic techniques are employed to study the binding of MTR to Mg++. These studies show : i) the drug alone binds to Mg++ and ii) two different types of drug-Mg++ complexes are formed at low (Complex I) and high (Complex II) ratios of the concentration of Mg++ and MTR. We propose that these two complexes would bind to the same DNA with different affinities and rates. This result suggests that the relative concentration of Mg++ is an important factor to be taken into account to understand the molecular basis of MTR-DNA interaction. © 1990 Academic Press, Inc.