Reduction of copper(II)-bleomycin: A model for in vivo drug activity

Jonathan H. Freedman, Susan Band Horwitz, Jack Peisach

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The effect of aliphatic thiols, including glutathione, cysteine, and dithiothreitol, on the anaerobic reduction of Cu(II)-bleomycin was examined. At neutral pH, cysteine is more efficient in reducing Cu(II)-bleomycin than either dithiothreitol or glutathione, while at alkaline pH the rate of reduction with all three reagents increases substantially. A kinetic treatment suggests that 2 equiv of thiol is required for each mole of Cu(II)-bleomycin reduced. Material balance studies verify this stoichiometry. If anaerobic reduction of Cu(II)-bleomycin is carried out in the presence of Fe(II), iron is chelated by the drug. This metal-drug complex is capable of degrading DNA when O2 is introduced. The extent of DNA degradation, as measured by the release of malondialdehyde-like chromogens from the DNA, is directly dependent on the amount of Cu(II)-bleomycin reduced.

Original languageEnglish (US)
Pages (from-to)2203-2210
Number of pages8
JournalBiochemistry
Volume21
Issue number9
StatePublished - 1982

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Bleomycin
Copper
Pharmaceutical Preparations
Dithiothreitol
Sulfhydryl Compounds
Glutathione
Cysteine
DNA
Coordination Complexes
Malondialdehyde
Stoichiometry
Iron
Metals
copper bleomycin
Degradation
Kinetics

ASJC Scopus subject areas

  • Biochemistry

Cite this

Reduction of copper(II)-bleomycin : A model for in vivo drug activity. / Freedman, Jonathan H.; Band Horwitz, Susan; Peisach, Jack.

In: Biochemistry, Vol. 21, No. 9, 1982, p. 2203-2210.

Research output: Contribution to journalArticle

Freedman, JH, Band Horwitz, S & Peisach, J 1982, 'Reduction of copper(II)-bleomycin: A model for in vivo drug activity', Biochemistry, vol. 21, no. 9, pp. 2203-2210.
Freedman, Jonathan H. ; Band Horwitz, Susan ; Peisach, Jack. / Reduction of copper(II)-bleomycin : A model for in vivo drug activity. In: Biochemistry. 1982 ; Vol. 21, No. 9. pp. 2203-2210.
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