Bleomycin metal complexes

Nucleic acid recognition by metal complexes of bleomycin 99CRV2797. 

The bleomycins (50) are hardly simple amines, but they do have two NH2 groups and a CONH2 group at the N-terminal domain, as well as potential donor nitrogens in pyrimidine and imidazole, which can complex metal ions." " The complexing of iron to bleomycin" " " has a significant effect on bleomycin-DNA interactions—metal complexes can mediate strand scission—and on alkene oxidation. Both may involve hydroperoxide intermediates." " " " ... 

RNA hydrolysis, 45 285-287, 297-299 metalloenzymes, 45 251-252 bleomycin, 45 252-260, 299 nucleic acid hydrolysis metal ions and, 45 283-285 by oligonucleotide modified with metal complexes, 45 297-299 of phosphodiesters, 45 251, 287-297 by ribozymes, 45 285-287 cleavage by iron bleomycin, 43 140 polymerase, arsonomethyl phosphonate analogue, 44 201-202 substructures, 43 133-134 transfer... 

Structural studies on bleomycin and its transition metal complexes 728... 

The bleomycins (Fig. 12.6) are a family of glycopeptide-derived antibiotics which are used in the treatment of various tumors. They bind iron in the blood and form an active hypervalent oxo-iron species. The two-dimensional structure is well known but no crystal structures of bleomycin or its metal complexes have been reported. The MM2 force field was modified and extended by modeling of the crystal structures of the cobalt complexes of two bleomycin analogues in order to develop a force field for... 

Barber et al. (61) have used FAB to study the antibiotics bleomycin A2 and B2 and their metal complexes. In particular, the ferrous sulfate complex of bleomycin A2 shows a pseudomolecular ion at mlz 1566, corresponding to the salt (A2 - H+ + FeS04) since the amide hydrogen of the histidine residue is lost on complexation. An ion at mlz 472 corresponds to the ferrous ion complexed to the surrounding ligands but lacking the disaccharide groups and the peptide chain. 

M. Barber, R. S. Bordoli, R. D. Sedgwick, A. N. Tyler, and B. V. Bycroft, Fast atom bombardment mass spectrometry of bleomycin A2 and B2 and their metal complexes, Biochemi. Biophysi. Res. Communi. 101 (1981), 632-638. 

Although the coordination and orientation of the metal complex are still not understood, extensive studies have been conducted concerning the remarkable chemistry of this species. The overall mechanism of action is described in Figure 8.19. In the presence of oxygen, the Fe(II) O2 species is formed and is likely rapidly converted to a ferric superoxide species. The one-electron reduction of this species, using either an organic reductant or another equivalent of Fe(II)-bleomycin, leads formally to an Fe(III)-peroxide, which then undergoes... 

The preceding FID analysis of several metallobleomycins verified that the DNA binding site-selectivities of Co(III) and Fe(III) bleomycin parallel each other quite closely and also correlate to the established cleavage site-selectivity of Fe(II) bleomycin + O2. Notably different, Cu(II) bleomycin did not exhibit an FID assay response under conditions used for the other metallobleomycins. This outcome was likely due to the weaker DNA binding and fast exchange of Cu(II) bleomycin relative to other metallobleomycins (48) and was no doubt exacerbated by the presence of a competitive binding fluorophore. In spite of this limitation, the FID assay is likely to contribute to the study of additional metal complex-DNA interactions in the future. 

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