Bleomycin
Glycopeptide antibiotic used as a chemotherapeutic agent that induces DNA strand breaks via metal-dependent oxidative cleavage.
Chemical Identity
| Property | Value |
|---|---|
| Chemical Formula | C55H84N17O21S3 |
| Molecular Weight | 1415.56 Da |
| CAS Number | 11056-06-7 |
| Peptide Class | Glycopeptide Antitumor Antibiotic |
| Origin | Streptomyces verticillus |
Structure
Bleomycin is a mixture of related glycopeptides (primarily A2 and B2) produced by Streptomyces verticillus. The molecule consists of a bithiazole moiety for DNA intercalation, a metal-binding domain with pyrimidine, beta-aminoalanine, and beta-hydroxyhistidine residues, and a terminal amine domain that varies between congeners.
Mechanism of Action
Bleomycin binds iron(II) and oxygen to form activated bleomycin, which generates superoxide and hydroxyl radicals that cleave DNA, preferentially at 5’-GC-3’ sequences. The bithiazole moiety intercalates into DNA, positioning the metal-oxo complex for strand scission. Bleomycin is cell-cycle specific for G2 and M phases.
Clinical Applications
- Hodgkin lymphoma: ABVD regimen component
- Testicular cancer: BEP regimen component
- Squamous cell carcinoma: Head, neck, cervix, penis
- Malignant pleural effusion: Intrapleural sclerosing agent
Pharmacokinetics
- Half-life: 2-4 hours (normal renal function)
- Distribution: Lung and skin (low bleomycin hydrolase activity)
- Metabolism: Bleomycin hydrolase (tissue-specific)
- Elimination: 60-70% renal
- Route: IV, IM, subcutaneous, intracavitary
Safety and Side Effects
Pulmonary fibrosis (dose-limiting, cumulative dose >400 units), skin hyperpigmentation, Raynaud’s phenomenon, mucositis, fever, and anaphylactoid reactions. Avoid supplemental oxygen when possible due to pulmonary toxicity risk.
References
- Umezawa, H., et al. (1966). Purification of bleomycin. Journal of Antibiotics, 19, 200-209.
- Blum, R.H., et al. (1973). Clinical review of bleomycin. Cancer, 31, 903-914.
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