Biopolymers and cell. 1999; 15 (2): 150 - 163

NMR analysis of the interaction of antibiotic daunomycin with deoxytetranucleotide, 5'-d(TpGpCpA), in aqueous solution

A. N. Veselkov, R. J. Eaton, S. F. Baranovsky, S. G. Osetrov, V. 1. Pahomov, P. A. Bolotin, L. N. Djimant, D. B. Davies

One-dimentional and two-dimentional (2D-TOCSY and 2D-NCJE-£Y) homonuclear H NMR spectroscopy and heteronuclear 2D- H-P-NMR spectroscopy have been used to investigate the comple-xation of the antibiotic daunomycin with deoxytetranucleotide S'-d(TpGpCpA) in aqueous salt solution. The equilibrium reaction constants, relative content of different types of complexes as a function of concentration and temperature of solution and thermo-dynamical parameters A# and AS of complexation of the molecules have been calculated using experimental concentrational and tempe¬rature dependences of the proton chemical shifts of the interacting molecules. Analysis of the results has shown that the most favou¬rable binding sites for daunomycin are triplet nucleotidc sequences. Binding of the second daunomycin molecule with both single-stranded and duplex forms of the tetranucleotide is highly anti- cooperative. The most favourable structure of 1:2 antibiotic-deoxy-tetranudeotide complex has been constructed using the calculated limiting proton chemical shifts of daunomycin protons in the' intercalated complex and 2D-NOE data.