A THEORETICAL-STUDY OF THE NONINTERCALATIVE BINDING OF BERENIL AND STILBAMIDINE TO DOUBLE-STRANDED (DA-DT)N OLIGOMERS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 25  (3) , 452-458
Abstract
The nonintercalative binding of 2 diarylamidines, berenil and stilbamidine, to the minor groove of double-stranded poly(A-T) oligomers in the B-DNA conformation was investigated by performing theoretical computations of their intermolecular interaction energies with the groove. The method consisted of an additive procedure developed previously in this laboratory using empirical formulae based on ab initio computations. The objective was to assess the extent to which the particular structure of each diarylamidine bears on its binding mode and affinity to the minor groove. The intrinsically preferred configurations of the 2 compounds were markedly different. Owing to its slightly curved shape, berenil interacted with the groove predominantly through its concave side, the binding occurring principally with sites (O2, O1'') belonging to 2 thymidines on the opposite strands. The binding of stilbamidine involved a more limited number of H-bonding interactions, although an appreciably large number of interatomic distances between its H and sites on the groove (O2, N3, O1'') fell in the range 2.7-3.1 .ANG.. Each side of stilbamidine with respect to its long axis faced a distinct strand of DNA. The importance of the electrostatic contribution of the binding energy of the 2 diarylamidines is underlined. Preferential binding of berenil rather than of stilbamidine occurred only at the level of a complete helical turn of P in poly(A-T). The energy difference increased significantly upon further buildup of P. These results can be interpreted in terms of the molecular electrostatic potential in the grooves.

This publication has 1 reference indexed in Scilit: