Interaction of Zn(II)bleomycin-A2 and Zn(II)peplomycin with a DNA hairpin containing the 5′-GT-3′ binding site in comparison with the 5′-GC-3′ binding site studied by NMR spectroscopy

Bleomycins are a group of glycopeptide antibiotics synthesized by Streptomyces verticillus that are widely used for the treatment of various neoplastic diseases. These antibiotics have the ability to chelate a metal center, mainly Fe(II), and cause site-specific DNA cleavage. Bleomycins are differentiated by their C-terminal regions. Although this antibiotic family is a successful course of treatment for some types of cancers, it is known to cause pulmonary fibrosis. Previous studies have identified that bleomycin-related pulmonary toxicity is linked to the C-terminal region of these drugs. This region has been shown to closely interact with DNA. We examined the binding of Zn(II)peplomycin and Zn(II)bleomycin-A2 to a DNA hairpin of sequence 5′-CCAGTATTTTTACTGG-3′, containing the binding site 5′-GT-3′, and compared the results with those obtained from our studies of the same MBLMs bound to a DNA hairpin containing the binding site 5′-GC-3′. We provide evidence that the DNA base sequence has a strong impact in the final structure of the drug–target complex.