Interactions among Iron (II) Bleomycin, Lewis Bases, and DNA

The interaction of sulfur-containing ligands with complexes of Fe(II) bleomycin [Fe(II)Blm] was investigated by comparing DNA strand-scission activity with the structural characteristics of the complex. The bithiazole ring of excess Blm can form intermolecular complexes with Fe(II)Blm and with NO-Fe...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1981-12, Vol.78 (12), p.7517-7520
Main Authors: Antholine, William E., Petering, David H., Saryan, Leon A., Brown, Charles Eric
Format: Article
Language:English
Subjects:
Biochemistry
Biomedical research
Biophysics
Bleomycin
Carbon Monoxide
Chemical equilibrium
DNA
Ferrous Compounds
Functional groups
Glutathione
Hydrolysis
Imidazoles
Ligands
Nitrous Oxide
Poly dA-dT
Protons
Rock cleavage
Structure-Activity Relationship
Thiols
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Summary:The interaction of sulfur-containing ligands with complexes of Fe(II) bleomycin [Fe(II)Blm] was investigated by comparing DNA strand-scission activity with the structural characteristics of the complex. The bithiazole ring of excess Blm can form intermolecular complexes with Fe(II)Blm and with NO-Fe(II)Blm, and the bithiazole groups of CO-Fe(II)Blm interact with the metal center. This binding can be reversed by glutathione. CO-Fe(II)Blm binds to poly(dA-dT)· poly(dA-dT) via its bithiazole group to change the environment of the Fe2+ion. Glutathione binds to the CO-Fe(II)Blm-poly(dA-dT)· poly(dA-dT) complex under conditions in which it stimulates DNA strand scission by Fe(II)Blm.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.78.12.7517