Chemistry of the Alkali-Labile Lesion Formed from Iron(II) Bleomycin and d(CGCTTTAAAGCG)

Hiroshi Sugiyama, Cheng Xu, Natesan Murugesan, Sidney M. Hecht, Jacques H. Van Boom, Gijs A. Van Der Marel

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

Two sets of products are formed from DNA upon treatment with Fe(II)·bleomycin + O2. One set, which is believed to derive from a C-4’ hydroperoxy derivative of the DNA deoxyribose moiety, includes the four possible base propenals, as well as DNA oligomers having deoxynucleoside 3’-(phosphoro-2“-O-glycolates) at their 3’-termini. The other set of products consists of free bases and alkali-labile lesions, the latter of which had not previously been characterized structurally. By use of the self-complementary dodecanucleotide d(CGCTTTAAAGCG) having a site modified by Fe•bleomycin three nucleotides from the 5’-end, it has been possible to characterize the alkali-labile product as a C-4’ hydroxyapurinic acid. When the bleomycin-treated dodecanucleotide was treated with agents that effected decomposition of the alkali-labile lesion, products of the form CpGpx were obtained, and these proved useful for structural characterization of the alkali-labile lesion. Treatment with alkali produced CpGpx, where x was 2,4-dihydroxycyclopentenone. Alternatively, treatment with hydrazine provided a pyridazine derivative, and aqueous alkylamines led to formation of CpGp itself. The structures of all dinucleotides produced from the alkali-labile lesion were verified by direct comparison with authentic synthetic samples.

Original languageEnglish (US)
Pages (from-to)58-67
Number of pages10
JournalBiochemistry
Volume27
Issue number1
DOIs
StatePublished - Jan 1 1988
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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  • Cite this

    Sugiyama, H., Xu, C., Murugesan, N., Hecht, S. M., Van Boom, J. H., & Van Der Marel, G. A. (1988). Chemistry of the Alkali-Labile Lesion Formed from Iron(II) Bleomycin and d(CGCTTTAAAGCG). Biochemistry, 27(1), 58-67. https://doi.org/10.1021/bi00401a011