Interchain cross-linking of DNA mediated by the principal adduct of acrolein

I. D. Kozekov, L. V. Nechev, A. Sanchez, C. M. Harris, Robert (Stephen) Lloyd, T. M. Harris

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Abstract

A DNA duplex containing the primary acrolein adduct, 3-(2-deoxy-β-D-erythro-pentofuranosyl)-5,6,7,8-tetrahydro-8- hydroxypyrimido[1,2-a]purin-10(3H)-one (2), of deoxyguanosine in a 5′-CpG sequence context spontaneously but reversibly formed an interchain cross-link with the exocyclic amino group of deoxyguanosine in the opposing chain. The linkage was sufficiently stable that the cross-linked duplex could be isolated by HPLC and characterized by MALDI-TOF mass spectrometry. Enzymatic degradation gave bis-nucleoside 6, which was independently prepared by direct reaction of 2 with dGuo.

Original languageEnglish (US)
Pages (from-to)1482-1485
Number of pages4
JournalChemical Research in Toxicology
Volume14
Issue number11
DOIs
Publication statusPublished - 2001
Externally publishedYes

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ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Kozekov, I. D., Nechev, L. V., Sanchez, A., Harris, C. M., Lloyd, R. S., & Harris, T. M. (2001). Interchain cross-linking of DNA mediated by the principal adduct of acrolein. Chemical Research in Toxicology, 14(11), 1482-1485. https://doi.org/10.1021/tx010127h