Biopolymers and cell. Volume 20. № 6. 479-492.

A. N. Veselkov, R. J. Eaton, V. I. Pahomov, O. V. Rogova, V. S. Volynkin, A. V. Semanin, L. N. Djimant, D. B. Davies

Distinctive features of the self-association of deoxyhexanucleotide 5¢-d(GpCpApTpGpC) and its complexation with anthracycline antibiotic daunomycin in aqueous solution

Summary

The self-association of self-complementary deoxyhexanucleotide 5¢-d(GpCpApTpGpC) and its complexation with antitumor antibiotic daunomycin have been investigated in aqueous solution using 1D- and 2D-¹H NMR correlation spectroscopy (2D-TOCSY and 2D-NOESY). Measurements of the concentration and temperature dependences of chemical shifts of nonexchangeable protons of deoxyhexanucleotide and daunomycin have been used to calculate the equilibrium constants and thermodynamical parameters (DH and DS) of d(GCATGC) duplex formation and complexation of the hexamer with the antibiotic. Based on the analysis of the proton chemical shifts of the hexamer at small concentrations and at relatively low temperatures, it has been assumed that the hexamer d(GCATGC) forms a compact structure (e.g. similar to a hairpin) in aqueous solution. The spatial structures of the hairpin and the intercalated complex of daunomycin with the duplex of the hexamer d(GCATGC) have been determined by molecular mechanics methods using X-PLOR software. Comparative analysis of the parameters of complex formation between antibiotic daunomycin and deoxyhexanucleotides of different base sequence has been made.