Recent Studies on Bleomycin
The structures of bleomycins, including their stereochemistry as shown in Figure 1, were conclusively determined by a study in the author’s institute in 1978 (Takita, Muraoka, Nakatani, Fujii, Umezawa, Naganawa & Umezawa, 1978b). The N-terminal amino acid contained in the bleomycin molecule was called pyrimidoblamic acid. Demethylpyrimidoblamylhistidylalanine which was thought to be a biosynthetic intermediate was isolated from a culture filtrate of a bleomycin-producing strain and its copper complex was crystallized. The structure of bleomycin shown in Figure 1 has been supported by crystal X-ray analysis and also by the chemical synthesis of pyrimidoblamic acid. Moreover, this structure has been confirmed by 15N-n.m.r. of bleomycin A2 (Naganawa, Takita, Umezawa & Hull, 1979) and also by mass spectroscopic analysis of bleomycins Bľ which gave the exact molecular weight of bleomycin (Macfarlane, Fujii, Takita & Umezawa, 1980). The main structural group common to all bleomycins is called bleomycinic acid (Figure 1). Bleomycinic acid consists of a peptide moiety, pyrimidoblamyl-β — hydroxy-histidyl- (4-amino-3-hydroxy-2-methyl) pentanoyl-thereonyl-2′- (2-aminoethyl)-2,4′-bithiazole-4-carboxylic acid, and a disaccharide part, 2-o-(3-o-carbamoyl-d-mannopyranosyl) -l-gulopyranoside. Bleomycin consists of bleomycinic acid and a terminal amine. As shown in Figure 1, various bleomycins which are different from one another in the terminal amine are produced by a bleomycin-producing strain. The present bleomycin used clinically consists mainly of bleomycins A2 and B2.
KeywordsFermentation Hull Alkaloid Hydrolase Bleomycin
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