Interaction of Bleomycin with Deoxyribonucleic Acid Oligomer: Proton Nuclear Magnetic Resonance Titration Study Using Novel Bleomycin Complexes with Ni2+ and V03+

Abstract

Two metal complexes of bleomycin (BLM), BLM-Ni2+ and BLM-VO3+ are used for studying interactions between BLM and deoxyribonucleic acid (DNA) by nuclear magnetic resonance. Although these BLMs do not mediate DNA strand scission under the usual conditions, they bind to DNA in the same manner as the active metal complexes of bleomycin (BLM-Fe2+ and BLM-Co3+). A self-complementary dodecanucleotide, d(CCCCAGCTGGGG), having a single site for cleavage was synthesized. d(CCCCAATTGGGG), which contains no -GpC- sequence, was also synthesized. The BLM-metal complexes were shown to bind specifically to the GpC site by circular dichroism and fluorescence titration studies. We assigned all the resonances for imino protons and phosphorus, and most of the nonexchangeable proton resonances of d(CCCCAGCTGGGG). No substantial change in the chemical shifts of these signals was observed upon titration with either BLM-Ni2+ or BLM-VO3+. This result is not consistent with a model of the strong intercalation of the BLMs between the base-pairs. The BLMs bind to DNA in a different manner, and DNA does not change its conformation upon binding with BLMs. © 1991, The Pharmaceutical Society of Japan. All rights reserved.