Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1981 Dec;78(12):7517–7520. doi: 10.1073/pnas.78.12.7517

Interactions among iron(II) bleomycin, Lewis bases, and DNA.

W E Antholine, D H Petering, L A Saryan, C E Brown
PMCID: PMC349299  PMID: 6174974

Abstract

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.

Full text

PDF
7517

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Antholine W. E., Petering D. H. On the reaction of iron bleomycin with thiols and oxygen. Biochem Biophys Res Commun. 1979 Sep 12;90(1):384–389. doi: 10.1016/0006-291x(79)91636-x. [DOI] [PubMed] [Google Scholar]
  2. Antholine W. E., Petering D. H. Reaction of FeBlm with DNA: Fe(II)Blm-NO. Biochem Biophys Res Commun. 1979 Nov 28;91(2):528–533. doi: 10.1016/0006-291x(79)91554-7. [DOI] [PubMed] [Google Scholar]
  3. Burger R. M., Peisach J., Blumberg W. E., Horwitz S. B. Iron-bleomycin interactions with oxygen and oxygen analogues. Effects on spectra and drug activity. J Biol Chem. 1979 Nov 10;254(21):10906–10912. [PubMed] [Google Scholar]
  4. Chen D. M., Sakai T. T., Glickson J. D., Patel D. J. Bleomycin-A2 complexes with poly(dA--dT): a proton nuclear magnetic resonance study of the nonexchangeable hydrogens. Biochem Biophys Res Commun. 1980 Jan 15;92(1):197–205. doi: 10.1016/0006-291x(80)91539-9. [DOI] [PubMed] [Google Scholar]
  5. Ishizuka M., Takayama H., Takeuchi T., Umezawa H. Activity and toxicity of bleomycin. J Antibiot (Tokyo) 1967 Jan;20(1):15–24. [PubMed] [Google Scholar]
  6. Kasai H., Naganawa H., Takita T., Umezawa H. Chemistry of bleomycin. XXII. Interaction of bleomycin with nucleic acids, preferential binding to guanine base and electrostatic effect of the terminal amine. J Antibiot (Tokyo) 1978 Dec;31(12):1316–1320. doi: 10.7164/antibiotics.31.1316. [DOI] [PubMed] [Google Scholar]
  7. Oppenheimer N. J., Rodriguez L. O., Hecht S. M. Structural studies of of "active complex" of bleomycin: assignment of ligands to the ferrous ion in a ferrous-bleomycin-carbon monoxide complex. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5616–5620. doi: 10.1073/pnas.76.11.5616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Povirk L. F. Catalytic release of deoxyribonucleic acid bases by oxidation and reduction of an iron.bleomycin complex. Biochemistry. 1979 Sep 4;18(18):3989–3995. doi: 10.1021/bi00585a023. [DOI] [PubMed] [Google Scholar]
  9. Sausville E. A., Peisach J., Horwitz S. B. A role for ferrous ion and oxygen in the degradation of DNA by bleomycin. Biochem Biophys Res Commun. 1976 Dec 6;73(3):814–822. doi: 10.1016/0006-291x(76)90882-2. [DOI] [PubMed] [Google Scholar]
  10. Sausville E. A., Peisach J., Horwitz S. B. Effect of chelating agents and metal ions on the degradation of DNA by bleomycin. Biochemistry. 1978 Jul 11;17(14):2740–2746. doi: 10.1021/bi00607a007. [DOI] [PubMed] [Google Scholar]
  11. Sausville E. A., Stein R. W., Peisach J., Horwitz S. B. Properties and products of the degradation of DNA by bleomycin and iron(II). Biochemistry. 1978 Jul 11;17(14):2746–2754. doi: 10.1021/bi00607a008. [DOI] [PubMed] [Google Scholar]
  12. Sheridan R. P., Gupta R. K. A 1H nuclear relaxation study of the Mn2+ . bleomycin complex. Proximity of the metal to the DNA-binding site. J Biol Chem. 1981 Feb 10;256(3):1242–1247. [PubMed] [Google Scholar]
  13. Solaiman D., Rao E. A., Petering D. H., Sealy R. C., Antholine W. E. Chemical, biochemical, and cellular properties of copper and iron bleomycins. Int J Radiat Oncol Biol Phys. 1979 Sep;5(9):1519–1521. doi: 10.1016/0360-3016(79)90762-4. [DOI] [PubMed] [Google Scholar]
  14. Sugiura Y., Kikuchi T. Formation of superoxide and hydroxy radicals in iron(II)-bleomycin-oxygen system: electron spin resonance detection by spin trapping. J Antibiot (Tokyo) 1978 Dec;31(12):1310–1312. doi: 10.7164/antibiotics.31.1310. [DOI] [PubMed] [Google Scholar]
  15. Umezawa H. Chemistry and mechanism of action of bleomycin. Fed Proc. 1974 Nov;33(11):2296–2302. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES