Bleomycin-copper chelates

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. 

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... 

Bleomycin is obtained as an equimolar complex with cupric ion. The copper can be removed by treatment with hydrogen sulfide in methanol solution to give a colorless metal-free BLM, which can be reconverted to the natural copper complex by addition of cupric ion to the aqueous solution, although there are many potential coordination sites in the molecule. Both metal-free and copper-chelated BLMs inhibited growth of microorganisms and mammalian cells, but DNA strand cleavage in vitro was caused only by metal-free BLM, not by the copper-complex. 

The metal binding ability of bleomycin was apparent from its isolation as the copper chelate, and derivatives of interest besides Cu and Fe (see... 

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. 

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