Copper(II).bleomycin, iron(III).bleomycin, and copper(II).phleomycin: comparative study of deoxyribonucleic acid binding

Publisher Website
Google Scholar
Abstract
The kinetics and mechanism of binding of Cu(II).cntdot.bleomycin, Fe(III).cntdot.bleomycin and Cu(II).cntdot.phleomycin [potential or actual anticancer antibiotics] to DNA were studied by using fluorometry, equilibrium dialysis, electric dichroism, and temperature-jump and stopped-flow spectrophotometry. The affinity of Cu(II).cntdot.bleomycin for DNA [from calf thymus or Escherichia coli] was greater than that of metal-free bleomycin but less than that of Fe(III).cntdot.bleomycin. Cu(II).cntdot.bleomycin exhibited a 2-step binding process, with the slow step indicating a lifetime of 0.1 s for the Cu(II).cntdot.bleomycin.cntdot.DNA complex. Fe(III).cntdot.bleomycin binding kinetics indicated the presence of complexes having lifetimes of up to 22 s. DNA was lengthened by 4.6 .ANG./molecule of bound Cu(II).cntdot.bleomycin and by 3.2 .ANG./bound Fe(III).cntdot.bleomycin but not at all by Cu(II).cntdot.phleomycin, suggesting that both bleomycin complexes intercalate while the phleomycin complex does not. Phleomycin exhibited nearly the same specificity of DNA base release as bleomycin. The coordinated metal ion may play a major role in the binding of metal-bleomycin complexes to DNA but that intercalation is neither essential for DNA binding and degradation nor primarily responsible for the specificity of DNA base release by these drugs.

This publication has 3 references indexed in Scilit: