Interaction of nogalamycin with DNA

Abstract

The binding of anti-tumour antibiotic nogalamycin with DNA has been investigated by equilibrium dialysis, spectrophotometric and viscometric methods. The dialysis and spectrophotometric measurements revealed a strong binding process with 0.14–0.16 binding sites available per nucleotide. The insignificant variation of the binding parameters with the ionic strength of the solvent proved that the binding process in this case was non-electrostatic in nature. Thermal denaturation of DNA also had no pronounced effect on the number of available binding sites or the binding affinity for the drug. The viscometric increment at different ionic strengths, nature of the melting profiles and the rise in the melting temperature were determined with increasing level of drug binding. These results confirmed the previous conclusions. Furthermore, a comparison of these results with those produced by the binding of proflavine showed that the nogalamycin side chain plays a significant role in stabilizing the double helix. An intercalation model for the DNA—nogalamycin complex was proposed earlier (Kersten, E., Kersten, H. and Szybalski, W. (1966) Biochemistry 5, 236–244). From the results of the present investigation, a modified intercalation model with the side chains incorporated into the neighbouring grooves has been suggested.