ESR studies on DNA cleavage induced by enediyne C-1027 chromophore

Toyonobu Usuki, Masayuki Inoue, Kimio Akiyama, Masahiro Hirama

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

C-1027 belongs to the family of chromoprotein antitumor antibiotics, which contain a carrier apoprotein and a highly unstable enediyne chromophore. The enediyne spontaneously aromatizes to generate p-benzyne biradical, and subsequently abstracts hydrogens from the DNA sugar backbone, resulting in cleavage of the double strand. Using spin-trapping methods, we obtained direct proof of radical intermediates during an DNA cleavage, and found intriguing difference in behavior between the trapping agents 2-methyl-2-nitrosopropane (MNP) and 5,5-dimethyl-1-pyrroline N-oxide (DMPO): MNP added to the sugar radicals of the DNA, whereas DMPO directly trapped a phenyl radical or p-benzyne biradical derived from the C-1027 chromophore.

Original languageEnglish
Pages (from-to)5218-5224
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume13
Issue number17
DOIs
Publication statusPublished - 2005 Sep 1

Keywords

  • Antitumor agents
  • DNA cleavage
  • ESR spectroscopy
  • Radicals

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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