Iron-bleomycin

To mimic the square-pyramidal coordination of iron bleomycin, a series of iron (Il)complexes with pyridine-containing macrocycles 4 was synthesized and used for the epoxidation of alkenes with H2O2 (Scheme 4) [35]. These macrocycles bear an aminopropyl pendant arm and in presence of poorly coordinating acids like triflic acid a reversible dissociation of the arm is possible and the catalytic active species is formed. These complexes perform well in alkene epoxidations (66-89% yield with 90-98% selectivity in 5 min at room temperature). Furthermore, recyclable terpyridines 5 lead to highly active Fe -complexes, which show good to excellent results (up to 96% yield) for the epoxidation with oxone at room temperature (Scheme 4) [36]. 

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... 

Burger RM, Kent TA, Horwitz SB, Munck E, Peisach J (1983) Mossbauer study of iron bleomycin and its activation intermediates. J Biol Chem 258 1559-1564 Burger RM, Freedman JH, Horwitz SB, Peisach J (1984) DNA degradation by manganese(l)-bleomy-cin plus peroxide. Inorg Chem 23 2215-2217... 

Burger RM, Projan SJ, Horwitz SB, Peisach J (1986) The DNA cleavage mechanism of iron-bleomycin. J Biol Chem 261 15955-15959... 

The natural product bleomycin mediates strand scission in the presence of iron and oxygen by a related mechanism (6, 12, 14) however, no diffusible intermediate is generated. Electrochemical and related studies showed that the mechanism of iron bleomycin (Fe-BLM) involves first reduction of Fe(III)-BLM, reaction of Fe(II)-BLM with 02, and reduction of the Fe(II)-BLM-02 adduct to activated Fe-BLM (15). 

J. W. Sam, X. J. Tang, J. Peisach, Electrospray mass spectrometry of iron bleomycin Demonstration that activated Bleomycin is a ferric peroxide complex, J. Am. Chem. Soc. 116 (1994) 5250. 

Iron bleomycin (FeBLM) is a natural product with anticancer activity that is thought to arise from nucleic acid damage and has been termed... 

Mascharak and co-workers have developed a synthetic analogue system for bleomycin (106, 109-112). In this system, the coordinating functions of BLM (alkyl amines, pyrimidine, peptide nitrogen, and imidazole) are combined in a minimal conf uration for modeling BLM within a ligand termed PMA". In addition to iron, bleomycin also coordinates copper and cobalt, and studies of these forms have been pursued as a source of new information on the physiologically relevant mechanism (17,18 96). The Cu(PMA) complex has been structurally characterized (Fig. 7) (109, 111), and its electronic properties mimic well those of Cu-BLM (113). As with Cu-BLM, a pH-dependent conformational equilihrium exists that interconverts Cu(PMA) with a di-... 

FIGURE 4.33 Mechanism of substrate oxidations in the presence of iron bleomycin, Fe (Blm).17,126... 

Fig. 4. Mechanism of the oxidative DNA cleavage by activated iron-bleomycin.

Although iron-bleomycin itself is well known for its sequence-specific ds-DNA cleaving abilities, it was also covalently bound to oligonucleotides, leading to cleavage of DNA [119], with the capability of performing multiple turnovers when... 

Bleomycin is a clinically useful family of glycopeptide antibiotic congeners with antitumoral activity. Cytotoxicity results from oxidative DNA damage. Bleomycin and transition metal ions form complexes that react with dioxygen and oxidize DNA. DNA damage is due to an activated form of iron bleomycin which forms from Fe -bleomycin in the presence of dioxygen and a source of electrons or from Fe -bleomycin in the presence of H2O2. 

In summary, manganese bleomycin is able to mediate DNA degradation in the presence of ascorbate (but not with 2-mercaptoethanol for an unknown reason) or iodosylbenzene. It is less efficient than its iron bleomycin congener. The detailed mechanism of the DNA damage by manganese bleomycin as well as the reason for its lower efficiency were not investigated. 

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