Bleomycin group antitumor agents

The bleomycins are structurally related antitumor antibiotics first isolated from Streptomyces verticillus as Cu(II) chelates by Umezawa and his colleagues. As illustrated in Figure 19.1, the bleomycins may be considered to be glycosylated oligopeptide-derived species, albeit composed of some rather unusual amino acid constituents. Some of these may actually be derived biosynthetically from proteinogenic amino acids, such as the bithiazole moiety, which is apparently formed by dehydrative cyclization and oxidation of β-alanylcysteinylcysteine. However, recent studies have revealed that the biosynthesis also depends in part on transformations used to assemble polyketide antibiotics.