Antibiotic-DNA interactions: intermolecular nuclear Overhauser effects in the netropsin-d(C-G-C-G-A-A-T-T-C-G-C-G) complex in solution.

Abstract

The proton markers located in the minor groove of the d(C-G-C-G-A-A-T-T-C-G-C-G) duplex and its netropsin complex were assigned from measurements of intramolecular nuclear Overhauser effects (NOEs) between exchangeable imino protons and nonexchangeable base protons on the same and adjacent base pairs. Several points of contact between the concave face of the antibiotic and the minor groove d(A-A-T-T) tetranucleotide segment of the dodecanucleotide duplex were established based on intermolecular NOE effects between the pyrrole ring and side-chain methylene protons of netropsin and the adenosine H-2 protons of dA.cntdot.dT base pairs in the center of the duplex. These NOE measurements provide a powerful method for differentiating between minor and major groove contacts in ligand-DNA complexes in solution. A model for netropsin interaction at dA.cntdot.dT sites on duplex DNA is proposed.