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 language | English (US) |
|---|---|
| Pages (from-to) | 2203-2210 |
| Number of pages | 8 |
| Journal | Biochemistry |
| Volume | 21 |
| Issue number | 9 |
| State | Published - 1982 |
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ASJC Scopus subject areas
- Biochemistry
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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 journal › Article
}
TY - JOUR
T1 - Reduction of copper(II)-bleomycin
T2 - A model for in vivo drug activity
AU - Freedman, Jonathan H.
AU - Band Horwitz, Susan
AU - Peisach, Jack
PY - 1982
Y1 - 1982
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0020327289&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0020327289&partnerID=8YFLogxK
M3 - Article
C2 - 6178433
AN - SCOPUS:0020327289
VL - 21
SP - 2203
EP - 2210
JO - Biochemistry
JF - Biochemistry
SN - 0006-2960
IS - 9
ER -