Chemistry of the alkali-labile lesion formed from iron(II) bleomycin and d(CGCTTTAAAGCG)

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

Research output: Contribution to journalArticle

90 Citations (Scopus)

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
StatePublished - 1988
Externally publishedYes

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Alkalies
hydrazine
Glycolates
DNA
Deoxyribose
Derivatives
Bleomycin
Oligomers
iron bleomycin
Nucleotides
Decomposition
Acids

ASJC Scopus subject areas

  • Biochemistry

Cite this

Sugiyama, H., Xu, C., Murugesan, N., Hecht, S., Van Der Marel, G. A., & Van Boom, J. H. (1988). Chemistry of the alkali-labile lesion formed from iron(II) bleomycin and d(CGCTTTAAAGCG). Biochemistry, 27(1), 58-67.

Chemistry of the alkali-labile lesion formed from iron(II) bleomycin and d(CGCTTTAAAGCG). / Sugiyama, Hiroshi; Xu, Cheng; Murugesan, Natesan; Hecht, Sidney; Van Der Marel, Gijs A.; Van Boom, Jacques H.

In: Biochemistry, Vol. 27, No. 1, 1988, p. 58-67.

Research output: Contribution to journalArticle

Sugiyama, H, Xu, C, Murugesan, N, Hecht, S, Van Der Marel, GA & Van Boom, JH 1988, 'Chemistry of the alkali-labile lesion formed from iron(II) bleomycin and d(CGCTTTAAAGCG)', Biochemistry, vol. 27, no. 1, pp. 58-67.
Sugiyama H, Xu C, Murugesan N, Hecht S, Van Der Marel GA, Van Boom JH. Chemistry of the alkali-labile lesion formed from iron(II) bleomycin and d(CGCTTTAAAGCG). Biochemistry. 1988;27(1):58-67.
Sugiyama, Hiroshi ; Xu, Cheng ; Murugesan, Natesan ; Hecht, Sidney ; Van Der Marel, Gijs A. ; Van Boom, Jacques H. / Chemistry of the alkali-labile lesion formed from iron(II) bleomycin and d(CGCTTTAAAGCG). In: Biochemistry. 1988 ; Vol. 27, No. 1. pp. 58-67.
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