Stimulation of Iron(II) Bleomycin Activity by Phosphate-Containing Compounds

Richard M. Burger, Susan Band Horwitz, Jack Peisach

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Orthophosphate and phosphate derivatives including pyrophosphate, hexametaphosphate, ATP, ADP, and inositol hexaphosphate enhance the extent of DNA degradation by iron(II) bleomycin. These phosphate-containing compounds increase both the release of free nucleic base and that of base propenals which are DNA cleavage products, probably by enhancing the efficiency with which Fe(II) is recruited into the drug. Phosphate action occurs during drug activation prior to the attack on DNA. In addition, phosphates affect the stability of the activated drug complex, overcome the inhibition observed with high concentrations of DNA, and reduce the size of the DNA fragment necessary for reacting with the drug. Phosrihate derivatives bind to iron(II) bleomycin and alter its optical spectrum. An analysis of titration data for pyrophosphate and inositol hexaphosphate indicates that each phosphate compound binds to more than one iron(II) bleomycin molecule. With ATP, ADP, and 2,3-diphosphoglycerate, only a single phosphate-containing compound binds to the ferrous drug complex. The affinity for ATP is sufficiently high as to suggest that the ternary complex formed in vitro may exist physiologically.

Original languageEnglish (US)
Pages (from-to)3623-3629
Number of pages7
JournalBiochemistry
Volume24
Issue number14
DOIs
Publication statusPublished - Jul 1 1985

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry

Cite this