Iron-bleomycin interactions with oxygen and oxygen analogues. Effects on spectra and drug activity

R. M. Burger, J. Peisach, W. E. Blumberg, Susan Band Horwitz

Research output: Contribution to journalArticle

106 Citations (Scopus)

Abstract

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 languageEnglish (US)
Pages (from-to)10906-10912
Number of pages7
JournalJournal of Biological Chemistry
Volume254
Issue number21
StatePublished - 1979

Fingerprint

Bleomycin
Oxygen
Pharmaceutical Preparations
Cyanides
DNA
Heme Oxygenase (Decyclizing)
Oxygenases
DNA Cleavage
Carbon Monoxide
Heme
Paramagnetic resonance
Iron
iron bleomycin
Association reactions
Oxidation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Iron-bleomycin interactions with oxygen and oxygen analogues. Effects on spectra and drug activity. / Burger, R. M.; Peisach, J.; Blumberg, W. E.; Band Horwitz, Susan.

In: Journal of Biological Chemistry, Vol. 254, No. 21, 1979, p. 10906-10912.

Research output: Contribution to journalArticle

@article{b8b00167c485470a8a3a77f0dfcaf190,
title = "Iron-bleomycin interactions with oxygen and oxygen analogues. Effects on spectra and drug activity",
abstract = "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.",
author = "Burger, {R. M.} and J. Peisach and Blumberg, {W. E.} and {Band Horwitz}, Susan",
year = "1979",
language = "English (US)",
volume = "254",
pages = "10906--10912",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "21",

}

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 - Band Horwitz, Susan

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.

UR - http://www.scopus.com/inward/record.url?scp=0018604135&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0018604135&partnerID=8YFLogxK

M3 - Article

C2 - 91607

AN - SCOPUS:0018604135

VL - 254

SP - 10906

EP - 10912

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 21

ER -