Jump to main content
Jump to site search

Issue 13, 2018
Previous Article Next Article

First characterisation of two important postulated intermediates in the formation of a HydT DNA lesion, a thymidine oxidation product

Author affiliations

Abstract

A number of environmental pollutants and endogenous oxidation agents form 1-(2-deoxy-β-D-ribofuranosyl)-5-hydroxy-5-methylhydantoin (HydT), an important DNA lesion resulting from thymidine oxidation. In this paper, two intermediates, postulated in the formation of HydT, have been characterised for the first time. The first, N1-formyl-N3-pyruvoylurea intermediate, was produced by the ozonolysis reaction of 2′,3′,5′-tri-O-acetylribo-, 3′,5′-di-O-TBS- and N3,O3′,O5-tribenzyl-protected thymidines and was shown to produce, upon decomposition and depending on the protecting group and the conditions, HydT alone, or together with protected-β-D-ribofuranosyl-N1-formylurea and formamide products. In addition, the second and long sought, open-chain-pyruvoylurea intermediate, was produced through de novo synthesis in protected β-D-ribofuranosyl-, 2-deoxy-β-D-ribofuranosyl- and 2-deoxy-β-D-ribopyranosyl systems. The conditions that induce the cyclization to the hydantoin ring of HydT have been determined. The chemistry utilised in the de novo synthesis is suitable for generating isotopically labelled HydT, as a reference in isotope-dilution-aided quantification of DNA damage.

Graphical abstract: First characterisation of two important postulated intermediates in the formation of a HydT DNA lesion, a thymidine oxidation product

Back to tab navigation

Supplementary files

Publication details

The article was received on 12 Feb 2018, accepted on 06 Mar 2018 and first published on 07 Mar 2018


Article type: Paper
DOI: 10.1039/C8OB00378E
Citation: Org. Biomol. Chem., 2018,16, 2289-2300
  •   Request permissions

    First characterisation of two important postulated intermediates in the formation of a HydT DNA lesion, a thymidine oxidation product

    E. E. Psykarakis, E. Chatzopoulou and T. Gimisis, Org. Biomol. Chem., 2018, 16, 2289
    DOI: 10.1039/C8OB00378E

Search articles by author

Spotlight

Advertisements