Bleomycins: towards better therapeutics.
Bleomycins are a family of glycopeptide antibiotics that have potent antitumour activity against a range of lymphomas, head and neck cancers and germ-cell tumours. The therapeutic efficacy of the bleomycins is limited by development of lung fibrosis. The cytotoxic and mutagenic effects of the bleomycins are thought to be related to their ability to mediate both single-stranded and double-stranded DNA damage, which requires the presence of specific cofactors (a transition metal, oxygen and a one-electron reductant). Progress in understanding the mechanisms involved in the therapeutic efficacy of the bleomycins and the unwanted toxicity and elucidation of the biosynthetic pathway of the bleomycins sets the stage for developing a more potent, less toxic therapeutic agent.
Chen
Jingyang
J
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Stubbe
JoAnne
J
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001692:Biological Transport; D001761:Bleomycin / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry; D004249:DNA Damage; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000235:genetics; D005355:Fibrosis; D006367:HeLa Cells; D006801:Humans; D008168:Lung / Q000473:pathology; D008954:Models, Biological; D008956:Models, Chemical; D008957:Models, Genetic; D008958:Models, Molecular; D009153:Mutagens; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism
D000900:Anti-Bacterial Agents; D004277:DNA, Single-Stranded; D009153:Mutagens; D001761:Bleomycin; D004247:DNA