title: Copper(I)-bleomycin: structurally unique complex that mediates oxidative DNA strand scission.
abstract: Copper(I)-bleomycin [Cu(I) X BLM] was characterized in detail by 13C and 1H NMR. Unequivocal chemical shift assignments for Cu(I) X BLM and Cu(I) X BLM X CO were made by two-dimensional 1H-13C correlated spectroscopy and by utilizing the observation that Cu(I) X BLM was in rapid equilibrium with Cu(I) and metal-free bleomycin, such that individual resonances in the spectra of BLM and Cu(I) X BLM could be correlated. The binding of Cu(I) by bleomycin involves the beta-aminoalaninamide and pyrimidinyl moieties, and possibly the imidazole, but not N alpha of beta-hydroxyhistidine. Although no DNA strand scission by Cu(II) X BLM could be demonstrated in the absence of dithiothreitol, in the presence of this reducing agent substantial degradation of [3H]DNA was observed, as was strand scission of cccDNA. DNA degradation by Cu(I) X BLM was shown not to depend on contaminating Fe(II) and not to result in the formation of thymine propenal; the probable reason(s) for the lack of observed DNA degradation in earlier studies employing Cu(II) X BLM and dithiothreitol was (were) also identified. DNA strand scission was also noted under anaerobic conditions when Cu(II) X BLM and iodosobenzene were employed. If it is assumed that the mechanism of DNA degradation in this case is the same as that under aerobic conditions (i.e., with Cu(I) X BLM + O2 in the presence of dithiothreitol), then Cu X BLM must be capable of functioning as a monooxygenase in its degradation of DNA.
authors.forename: G M
authors.initials: GM
authors.lastname: Ehrenfeld
authors.forename: L O
authors.initials: LO
authors.lastname: Rodriguez
authors.forename: S M
authors.initials: SM
authors.lastname: Hecht
authors.forename: C
authors.initials: C
authors.lastname: Chang
authors.forename: V J
authors.initials: VJ
authors.lastname: Basus
authors.forename: N J
authors.initials: NJ
authors.lastname: Oppenheimer
mesh_terms: D001761:Bleomycin / Q000031:analogs & derivatives; D003300:Copper; D004279:DNA, Viral; D004229:Dithiothreitol; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D010084:Oxidation-Reduction; D013539:Simian virus 40
chemical_list: D004279:DNA, Viral; C023502:copper bleomycin; D001761:Bleomycin; D003300:Copper; D004229:Dithiothreitol