Kinetics and stereoselectivity of thiol trapping of deoxyuridin-1'-yl in biopolymers and their relationship to the formation of premutagenic α- deoxynucleotides

Jae Taeg Hwang, Marc M. Greenberg

Research output: Contribution to journalArticlepeer-review

Abstract

α-Deoxynucleotides are potentially deleterious lesions when produced in DNA. They are presumably formed in part via misrepair of the respective C1'- nucleotide radicals by thiols. However, the selectivity and extent to which these lesions are formed via this pathway has not been ascertained. Using the ability to independently generate deoxyuridin-1'-yl (4) at a defined site in a biopolymer, we have determined that thiol trapping in duplex DNA occurs with high stereoselectivity from the α-face, resulting in restoration of the naturally occurring β-deoxynucleotide. The observed stereoselectivity of thiol trapping in duplex DNA suggests that 4 is intrahelical. The rate constant for hydrogen atom donation to 4 is reduced 2-3-fold in double- stranded DNA compared to single-stranded DNA. This decrease is attributed to the relative inaccessibility of the C1'-position in duplex DNA. The combination of these two properties of 4 indicates that, at O2 concentrations present in aerated water, α-deoxynucleotide formation should constitute a minor component of the reactivity of C1'-radicals. Accordingly, the chemical biology of other lesions derived from formal damage at C1'- position could be significant.

Original languageEnglish (US)
Pages (from-to)4311-4315
Number of pages5
JournalJournal of the American Chemical Society
Volume121
Issue number18
DOIs
StatePublished - May 12 1999
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry

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