Interaction of Zn(II)bleomycin-A 2 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 differen...

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Bibliographic Details
Published in:Journal of biological inorganic chemistry 2017-10, Vol.22 (7), p.1039
Main Authors: Follett, Shelby E, Ingersoll, Azure D, Murray, Sally A, Reilly, Teresa M, Lehmann, Teresa E
Format: Article
Language:English
Subjects:
Antibiotics, Antineoplastic - chemistry
Antibiotics, Antineoplastic - pharmacology
Binding Sites
Bleomycin - analogs & derivatives
Bleomycin - pharmacology
DNA - chemistry
DNA - metabolism
Humans
Neoplasms - drug therapy
Neoplasms - metabolism
Nuclear Magnetic Resonance, Biomolecular
Peplomycin - analogs & derivatives
Peplomycin - pharmacology
Zinc - chemistry
Zinc - pharmacology
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Summary: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-A 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.
ISSN:1432-1327