Photoactivated DNA cleavage by compounds structurally related to the bithiazole moiety of bleomycin

James C. Quada, Didier Boturyn, Sidney Hecht

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The syntheses of several novel halogenated bithiazoles structurally related to the bithiazole moiety of bleomycin A5 are described. Also described is the ability of these compounds to mediate photoactivated NA cleavage. Chlorinated bithiazole analogues were shown to be much more active than an analogous brominated derivative. DNA strand scission activity was strictly light dependent and was accompanied by dechlorination of the bithiazole nucleus, apparently in a stoichiometric fashion. Inhibition of DNA cleavage in the presence of DMSO, as well as photoaddition to 1-octene by both brominated and chlorinated bithiazole derivatives, suggest strongly that the initial step in photoactivated DNA cleavage involves homolysis of the thiazole carbon-haloge bond. The chlorinated bithiazoles were found to mediate sequence selective cleavage of a 32P-end labeled DNA, although the selectivity observed was not the same as that of bleomycin itself. The implications of this observation are discussed.

Original languageEnglish (US)
Pages (from-to)2303-2314
Number of pages12
JournalBioorganic and Medicinal Chemistry
Volume9
Issue number9
DOIs
StatePublished - 2001
Externally publishedYes

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DNA Cleavage
Bleomycin
Thiazoles
DNA
Dimethyl Sulfoxide
Carbon
Derivatives
Light
Dechlorination
bleomycetin
1-octene

ASJC Scopus subject areas

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

Cite this

Photoactivated DNA cleavage by compounds structurally related to the bithiazole moiety of bleomycin. / Quada, James C.; Boturyn, Didier; Hecht, Sidney.

In: Bioorganic and Medicinal Chemistry, Vol. 9, No. 9, 2001, p. 2303-2314.

Research output: Contribution to journalArticle

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