Copper bleomycin

In 400 ml of dimethylformamide was dissolved 15.0 g of bleomycinic acid (copper-containing form). To the solution kept at 0°C by cooling were added 1.1 ml of N-methylmorpholine and 10.3 g of 6-chloro-1 -p-chlorobenzenesulfonyloxybenzotriazole (CCBT) as an activating compound. The mixture was stirred for 5 minutes at 0°C, then admixed with 5.3 g of N-[(S)-1 -phenylethyl] -1 3-diaminopropane and further stirred for 1 hour. 

By similar treatment, 280 mg of the unreacted bleomycinic acid (copper-containing form) were recovered. 

Umezawa, H., Takita, T.. The Bleomycins Antitumor Copper-Binding Antibiotics. Vol. 40, pp. 73-99. 

Petering, D. Xiao, J. Nyayapati, S. Fulmer, P. Antholine, W. Oxidation Damage by Bleomycin, Adriamycin and Other Cytotoxic Agents that Require Iron or Copper Farrell, N., Ed. The Royal Society of Chemistry Cambridge,... 

Bleomycin (BLM) was first isolated as a copper complex from a culture of Streptomyces verticillus. Since then numerous analogs have been prepared by modifying the conditions of fermentation. Bleomycins (114, bleomycin A2) are used clinically in combination cancer chemotherapy for the treatment of head and neck cancer, certain lymphomas, and testicular cancer (555). 

In 1972, we elucidated the structure of bleomycin except for the side-chain part of the pyrimidoblamyl moiety (53), and in 1978, we determined the structtire of bleomycin conclxosively, as is shown in Fig. 4 (52). One of the amino acids contained in bleomycin has a pyrimidine ring we named this amino acid "pyrimldo-blamic acid". During the study of biosynthesis, demethylpyrimi-doblamylhistidinylalanine was obtained and its copper complex was crystallized. Based on the x-ray analysis of this crystal (10), we proposed the strvxiturej gf bleomycin in Fig. 4. We also confirmed this structure by N-nmr (25). 

In the presence of ferrous ions and oxygen, copper-free bleomycin causes a double-stremd scission of The bleomycin-Cu ... 

Another agent which has found application in tumor imaging is luIn-bleomycin.505 The bleomycins are naturally occurring water-soluble copper-containing glycopeptide antibiotics having the generic structure (42), in which R may be a variety of substituent as shown in Table 23.723... 

H. Umezawa, T. TaMta The Bleomycins Antitumor Copper-Binding Antibiotics(57 ref.)... 

Bleomycin Bleomycin is incompatible and loses its potency if it is administered with solutions of benzylpenicillin sodium, carbenicillin, cephazolin or cephalothin sodium, hydrocortisone sodium succinate, mitomycin, methotrexate, nafcillin sodium, aminophylline, ascorbic acid, terbutaline, divalent and trivalent cations (especially copper), compounds containing sulfhydryl groups, and precipitation by hydrophobic anions, essential amino acids, riboflavine, dexamethasone, and frusemide. 

Bleomycin [blee oh MYE sin] is a mixture of different copper chelating glycopeptides that, like the anthracycline antibiotics, cause scission of DNA by an oxidative process. 

T. Takita The Bleomycins Antitumor Copper-Binding Antibiotics. 

Analogs of the metal-chelating center of bleomycin, which is a glycopeptide antibiotic, have been synthesized and the stmctmes of their copper(II) complexes have been determined. These complexes show similar bonding as bleomycin. The copper is in a highly distorted enviromnent approaching square pyramidal, with 3N coordination that includes coordination by an imidazole nitrogen. 

Maruyama M, Kumagai T, Matoba Y, Hayashida M, Fujii T, Hata Y, Sugiyama M. Crystal structures of the transposon Tn5-carried bleomycin resistance determinant uncomplexed and complexed with bleomycin. J. Biol. Chem. 2001 276(13) 9992—9999. Sugiyama M, Kumagai T, Hayashida M, Maruyama M, Matoba Y. The 1.6-A crystal structure of the copper(II)-bound bleomycin complexed with the bleomycin-binding protein from bleomycin-producing Streptomyces verticillus. J. Biol. Chem. 2002 277(3) 2311-2320. 

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