Biopolymers and cell. 2003; 19 (6): 504 - 512

2D H-NMR analysis of complexation of phenoxazone compound actinocyl-bis-(2-dimethylaminoethyl) amide with deoxytetranucleotide 5'-d(TpGpCpA) in aqueous solution

A. N. Veselkov, R. J. Eaton, A. O. Lantushenko, O. V. Rogova, A. Hernandez Santiago, D. B. Davies

Complexation of a synthetic phenoxazone compound actinocyl-bis-(2-dimethylaminoethyl) amide (Actll) with self-complementary deoxytetranucleotide S'-d(TpGpCpA) in aqueous solution has been studied by two-dimensional 1H-NMR spectroscopy (500 MHz). Two-dimensional homonuclear correlation NMR spectroscopy (2D-TOCSY and 2D-NOESY) has been used for complete assignment of proton signals of phenoxazone compound and nucleotides in the mixed solution and for determining the structure of the intercalated complex of Actll with the tetramer duplex. Analysis of inter-molecular NOE-contacts enables to conclude that Actll preferentially intercalates into the terminal d(TG)-site of the tetranucleotide and to propose the most favourable spatial structures of Actll-d(TpGpCpA) complexes. It follows that aminoalkyl side chains of Actll are situated in the minor groove of the tetramer duplex.