DIFFERENTIAL INHIBITION OF DNA-PROTEIN INTERACTIONS BY AROMATIC AMIDINES WITH 2-BENZAMIDINE, 3-BENZAMIDINE AND 4-BENZAMIDINE RESIDUES

We have recently reported that aromatic polyamidines are powerful inhi bitors of in vitro proliferation of tumour cell lines and in vivo tumo rigenicity of melanoma cells xenografted into nude mice. Interestingly , we have found that tetra-benzamidines are able to bind DNA, and to i nhibit the interaction between transacting factors and specific target DNA sequences. In order to obtain more detailed information on struct ure-activity relationships, we have analysed the effects of different aromatic polyamidines on the binding of a recombinant protein, the Eps tein-Barr virus (EBV) nuclear antigen 1 (EBNA-1), to the target sequen ce of EBV DNA, containing the 12 bp palindromic consensus TAGCATATGCTA . The results obtained suggest that aromatic polyamidines inhibit the interactions between DNA-binding proteins and target DNA sequences wit h different efficiency, depending (i) on the number of amidine residue s and (ii) on the presence of halogen substitutions (Cl, Br or I) on t he benzene rings of tetra-benzamidine molecules.