ABSTRACT
A typical approach to investigating metal ion requirements for cellular activity has been to add to the system metal chelating agents that supposedly bind to a particular metal ion and look for changes in drug action. There are surprisingly few established examples of metal-requiring antibiotics and fewer still which have been unequivocally shown to bind metal ions directly as part of their mechanism of action. Bleomycin is a structurally complicated natural product released by Streptomyces verticillus into its environment as an antibiotic. The principal interest in bleomycin (Blm) and related compounds lies in its strong antineoplastic properties. It is now evident that every part of the Blm structure plays a role in achieving its biological activity; its complexity stands as a reminder of the subtlety with which nature works. A Dox semi-quinone free radical was generated in the reaction and may have served as a direct or indirect reducing agent for membrane-associated Fe(III).
