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  • Title: Role of Mg++ in the mithramycin-DNA interaction: evidence for two types of mithramycin-Mg++ complex.
    Author: Aich P, Dasgupta D.
    Journal: Biochem Biophys Res Commun; 1990 Dec 14; 173(2):689-96. PubMed ID: 2148084.
    Abstract:
    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.
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