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Self-inactivation of Fe(II)-bleomycin.
1Department of Molecular Pharmacology, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461.
The Journal of Antibiotics
|May 1, 1988
Summary
The self-inactivated form of Fe(II)-Bleomycin loses DNA cleavage ability due to chemical changes, as evidenced by altered fluorescence and EPR spectroscopy. This study details its preparation and properties.
Area of Science:
- Biochemistry
- Molecular Biology
- Drug Discovery
Background:
- Fe(II)-Bleomycin is an active DNA-cleaving agent when complexed with Fe(II) and oxygen.
- The drug's activity is dependent on the presence of DNA, leading to self-inactivation in its absence.
Purpose of the Study:
- To describe a method for preparing and purifying the self-inactivated Fe(II)-Bleomycin.
- To investigate the physical properties and chemical changes associated with the loss of DNA cleavage activity.
Main Methods:
- Preparation and purification of self-inactivated bleomycin A2.
- Analysis of physical properties, including bithiazole fluorescence.
- Electron Paramagnetic Resonance (EPR) spectroscopy to study metal binding sites.
Main Results:
- A method for obtaining self-inactivated bleomycin was established.
- Loss of DNA cleavage activity correlated with altered bithiazole fluorescence, indicating chemical modification.
- EPR studies confirmed the copper(II) binding site remains intact and the ability to form an activated-like species with Fe(II)/O2 is preserved.
Conclusions:
- Self-inactivation of Fe(II)-Bleomycin involves chemical alteration of the bithiazole moiety.
- Despite inactivation, the fundamental metal-binding and spectroscopic properties relevant to activation are retained.