Abstract

Bleomycin is a clinically useful antitumor antibiotic employed for the treatment of squamous cell carcinomas and malignant lymphomas. Bleomycin can form several redox-active metal complexes that are capable of DNA strand scission and it is this oxidative transformation that is believed to be responsible for its utility as an antitumor agent. The objectives of this study are a better understanding of the way in which bleomycin is activated, the chemical nature of the activated intermediate(s) and the mechanism by which activated bleomycin mediates DNA degradation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA038544-02
Application #
3176597
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1984-12-01
Project End
1987-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Virginia
Department
Type
Schools of Arts and Sciences
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904

  Publications

Hecht, S M (1994) RNA degradation by bleomycin, a naturally occurring bioconjugate. Bioconjug Chem 5:513-26
Kane, S A; Hecht, S M (1994) Polynucleotide recognition and degradation by bleomycin. Prog Nucleic Acid Res Mol Biol 49:313-52
Holmes, C E; Carter, B J; Hecht, S M (1993) Characterization of iron (II).bleomycin-mediated RNA strand scission. Biochemistry 32:4293-307
Carter, B J; Murty, V S; Reddy, K S et al. (1990) A role for the metal binding domain in determining the DNA sequence selectivity of Fe-bleomycin. J Biol Chem 265:4193-6
Carter, B J; de Vroom, E; Long, E C et al. (1990) Site-specific cleavage of RNA by Fe(II).bleomycin. Proc Natl Acad Sci U S A 87:9373-7
Sugiyama, H; Xu, C; Murugesan, N et al. (1988) Chemistry of the alkali-labile lesion formed from iron(II) bleomycin and d(CGCTTTAAAGCG). Biochemistry 27:58-67
Shipley, J B; Hecht, S M (1988) Bleomycin congeners exhibiting altered DNA cleavage specificity. Chem Res Toxicol 1:25-7
Levy, M J; Hecht, S M (1988) Copper(II) facilitates bleomycin-mediated unwinding of plasmid DNA. Biochemistry 27:2647-50
Ehrenfeld, G M; Shipley, J B; Heimbrook, D C et al. (1987) Copper-dependent cleavage of DNA by bleomycin. Biochemistry 26:931-42
Hecht, S M (1986) DNA strand scission by activated bleomycin group antibiotics. Fed Proc 45:2784-91

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