Despite extensive structural dissimilarities, iron-bleomycin complexes and heme-containing oxygenases display remarkable similarities in binding oxygen antagonists and in spectral properties deriving from bound iron. Fe(II)-bleomycin reversibly forms a complex with either CO or isocyanide (λ(max)=384 and 497 nm, respectively), either of which interfere with its oxygen-dependent cleavage of DNA. A similar but paramagnetic complex forms with NO (λ(max) = 470 nm; A(N) = 24 G). In contrast, cyanide enhances bleomycin activity against DNA. Complexes of bleomycin and Fe(III), formed either by direct association or by autoxidation of the Fe(11)-bleomycin complex, exhibit indistinguishable EPR and visible spectra, which change characteristically with pH. At neutral pH, Fe(111)-bleomycin is a low spin complex (g = 2.45, 2.18, 1.89; αl(max) = 365, 384 nm) and, at low pH, it is a high spin rhombic complex (g(eff) = 9.4, 4.3; λ(max) = 430 nm). These complexes are interconvertible (pK 4.3). Fe(11)-bleomycin oxidation, although reversible by spectral criteria, is accompanied by drug inactivation unless DNA is present.
|Original language||English (US)|
|Number of pages||7|
|Journal||Journal of Biological Chemistry|
|State||Published - Dec 1 1979|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology