1H‐NMR studies of the interaction between a self‐complementary deoxyoligonucleotide duplex and indolo[2,3‐b]quinoxaline derivatives active against herpes virus

Abstract

1H NMR has been used to study the interactions of ellipticine and the ellipticine analogues 2-3-dimethyl-6-(2-dimethylaminoethyl)6H-indolo-[2,3-b]quinoxaline and 6-(2-dimethylaminoethyl)6H-indolo-[2,3-b]quinoxaline with the self-complementary decadeoxyribonucleotide d(CGCGATCGCG)2. The Watson-Crick H-bonded imino proton resonances were studied. The drugs were shown to bind to the duplex by intercalation involving slow exchange kinetics for the imino proton resonances on the NMR time scale (500 MHz). Ellipticine and the 2,3-dimethyl analogue were found not to show strong base preferences, while the other analogue was found to have a preferred primary binding site between the A.T base pairs with a probable minor secondary binding site between the A.T and adjacent G.C base pairs. The new drug-shifted imino proton resonances were assigned through saturation transfer experiments. The base-specific interactions were accompanied by drug-induced non-uniform broadening of the resonances (due to intermediate chemical exchange kinetics), in the spectral region of the non-exchangeable aromatic and sugar H1' proton resonances of the oligonucleotide at 25 degrees C.