Bleomycin complex

The presently accepted model1555 for the reaction of bleomycin with DNA involves the binding of an Fen-bleomycin complex to DNA, and the reduction of iron-bound dioxygen. Cleavage of DNA is known to occur by the action of the 1,10-phenanthroline complex of Cu1 in the presence of hydrogen peroxide, and this reaction is sustained by the presence of NADH.1556 This provides a useful parallel for the bleomycin reaction. 

Chakrabarti S, Makrigiorgos GM, O Brien PJ, Bump E, Kassis Al (1996) Measurement of hydroxyl radicals catalyzed in the immediate vicinity of DNA by metal-bleomycin complexes. Free Rad Biol Med 20 777-783... 

The antitumour action of the natural antibiotic bleomycin is thought to involve the aerobic degradation of DNA by the Fe2+-bleomycin complex. In order to probe the mechanism of antitumour action of bleomycin, the 4-ethylamido[5,(2 -thienyl)-2-thiophene] imidazole iron(II) complex was synthesized [129]. It was studied in non-aqueous solution using cyclic voltammetry and showed antitumour activity in vitro, its action causing cleavage of the double helical DNA. 

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. 

Bleomycins and their analogues occur naturally as blue copper chelates. Removal of the copper by chemical reduction or complexing agents affords the antibiotics as white solid.s. Copper-free bleomycin is the active. species for chemotherapy, and it has lower toxicity. Bleomycin complexes readily with metal ion.s. which is a key factor in its mode of action. In.sidc the cell, bleomycin forms a chclatc with Fe(ll) that has square pyramidal gcomctiy. Nitrogen atoms from bleomycin occupy five of the po.sitions in this structure. The sixth position may be occupied by the carboxyl group of the carhamate function, but this group is... 

Fig. 1. CM-Sephadex C-2S chromatography of bleomycin complex isolated from the cultured broth...

L.M. (1990) Stable [57Co]-bleomycin complex with a very high specific radioactivity for use at very low concentrations. Biochemical and Biophysical Research Communications, 173, 259-264. 

The interaction of bleomycin with metal ions and the chemistry associated with this interaction has been the focus of numerous studies aimed at elucidating the detailed mechanism of action of this drug. A recent paper notes that the interaction of bleomycin with iron gives a reactive intermediate which cleaves DNA. Ferrous ion-bleomycin interaction results in chemiluminescence suggesting that the activated intermediate may be electronically excited, Mossbauer studies of the ferrous and ferric bleomycin complexes indicated that the latter complex may exist in two distinct conformations. In a study of cobalt-bleomycin complexes, the existence of a cobalt-bleomycin-hydroperoxide complex capable of nicking DNA has been demonstrated. ... 

A combined TLC/FAB m.s. technique has been developed for Identifying the components of the bleomycin complex (these contain an... 

Skin, eye and respiratory tract irritant. Possible human carcinogen (applies to Bleomycin complex). Pulmonary toxicity reported when used therapeutically. LD50 (mus, ipr) 130 mg/kg LD50 (mus, ivn) 120 mg/kg. EC5988500... 

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