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Complexation of daunomycin with a DNA oligomer in the presence of an aromatic vitamin (B2) determined by NMR spectroscopy.

Evstigneev MP, Mykhina YV, Davies DB

Department of Physics, Sevastopol National Technical University, Studgorodok, Sevastopol, 99053, Crimea, Ukraine. max_evstigneev@mail.ru

The effect of simultaneous binding of the anthracycline antibiotic Daunomycin (DAU) and the Vitamin B2 derivative, Flavin-mononucleotide (FMN), with the DNA oligomer, d(TGCA)2, in solution has been investigated quantitatively by 1I-NMR spectroscopy (500 MHz). The equilibrium reaction constants and the thermodynamical parameters (DeltaH, DeltaS) of the hetero-association FMN-DAU and complexation of FMN with d(TGCA)2 have been determined by analysis of the concentration and temperature dependences of chemical shifts of the aromatic protons in terms of a competitive binding model. A criterion for discrimination between hetero-association and DNA complexation has been developed and applied to the analysis of the simultaneous binding of the antibiotic and the vitamin with DNA. Under the conditions of the experiment, it is found that both the hetero-association of FMN with DAU and the complexation of FMN with DNA contribute approximately equally to the decrease of DAU binding with DNA oligomer. Such competitive complexation of aromatic vitamin and drug with DNA could affect the biological activity of such drugs.

Published 18 November 2005 in Biophys Chem, 118(2): 118-27.
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