Abstract

This proposal seeks to renew support for studies the long term goal of which exact definition of the molecular mechanism(s) by which bleomycin exerts its effects as an antitumor agent. For the period of requested support, it is proposed to: . study the orientation of BLM on the DNA duplex and the way in which double strand cleavage is mediated . analyze the role of metal ions in BLM ligation and DNA binding . study the effects of altered DNA structure on susceptibility to BLM cleavage . characterize the chemical nature of activated metallobleomycins and the way in which oxygen is transferred to olefinic substrates.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37CA038544-06
Application #
3482411
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1984-12-01
Project End
1992-11-30
Budget Start
1989-12-01
Budget End
1990-11-30
Support Year
6
Fiscal Year
1990
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

Showing the most recent 10 out of 12 publications