TY - JOUR
T1 - Iron-bleomycin interactions with oxygen and oxygen analogues. Effects on spectra and drug activity
AU - Burger, R. M.
AU - Peisach, J.
AU - Blumberg, W. E.
AU - Horwitz, S. B.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1979
Y1 - 1979
N2 - 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.
AB - 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.
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M3 - Article
C2 - 91607
AN - SCOPUS:0018604135
SN - 0021-9258
VL - 254
SP - 10906
EP - 10912
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 21
ER -