Abstract

Bleomycin (BLM) is a group of glycopeptide antibiotics produced by Streptomyces verticillus. It is now clinically used for the treatment of squamous cell carcinoma, malignant lymphoma etc. BLM is isolated as blu-colored amorphous powder from the cultured broth. It is an equimolar copper-complex. The biosynthesis study suggested that the peptide chain of BLM is formed by thiotemplate mechanism and the copper is essential for the biosynthesis of BLM. The definitive structure of metal-free BLM has been established recently by chemical study. Very recently the structure of copper-complex of BLM was investigated by chemical study and X-ray crystallographic analysis of an biosynthetic intermediate of BLM. The primary action of BLM responsible for the bioactivity appears to be DNA cleavage. For the cleavage of DNA in vitro, the presence of ferrous ion and molecular oxygen was found to be essential. Interaction of BLM and DNA was studied by fluoresence spectroscopy and the nucleotide sequence preferentially cleaved by BLM was studied by a new method developed by Maxam and Gilbert. The mode of action of BLM in a molecular lever may be explained by reaction of the reductively activated oxygen at the sixth coordination site of BLM-Fe(II)-complex with DNA.

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