INTERACTION OF THE COBALT COMPLEX OF A BLEOMYCIN FUNCTIONAL-MODEL WITH D(CGCAATTGCG)(2) - EVIDENCE OF MINOR-GROOVE BINDING BY 2D NMR METHODS

The interaction between the cobalt complex of a bleomycin functional m odel and d(CGCAATTGCG)(2) was determined by 2D NMR methods. The interm olecular NOE cross peaks between ligand protons and the DNA minor groo ve protons suggest that the cobalt complex of AMPHIS-NET binds in the minor groove of DNA at the central AATT site. Also, the NOEs interacti ons of H-8 pyridine proton and H-2 imidazole proton in the metal-bindi ng domain with H-4' sugar proton of C9 and H-4' sugar proton of A15 de monstrate that the sixth ligand site of cobalt complex, which is occup ied by a solvent molecule, faces towards the minor groove of DNA. This binding model is in accord with the observed non-diffusion DNA cleava ge by the metal-complexes of the bleomycin functional model compounds. (C) 1995 Academic Press, Inc.