Fragmentation of electrospray-produced deprotonated ions of oligodeoxyribonucleotides containing an alkylated or oxidized thymidine

Pengcheng Wang, Renee T. Williams, Candace R. Guerrero, Debin Ji, Yinsheng Wang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

(Graph Presented) Alkylation and oxidation constitute major routes of DNA damage induced by endogenous and exogenous genotoxic agents. Understanding the biological consequences of DNA lesions often necessitates the availability of oligodeoxyribonucleotide (ODN) substrates harboring these lesions, and sensitive and robust methods for validating the identities of these ODNs. Tandem mass spectrometry is well suited for meeting these latter analytical needs. In the present study, we evaluated how the incorporation of an ethyl group to different positions (i.e., O2, N3, and O4) of thymine and the oxidation of its 5-methyl carbon impact collisionally activated dissociation (CAD) pathways of electrospray-produced deprotonated ions of ODNs harboring these thymine modifications. Unlike an unmodified thymine, which often manifests poor cleavage of the C3′-O3′ bond, the incorporation of an alkyl group to the O2 position and, to a much lesser extent, the O 4 position, but not the N3 position of thymine, led to facile cleavage of the C3′-O3′ bond on the 3′ side of the modified thymine. Similar efficient chain cleavage was observed when thymine was oxidized to 5-formyluracil or 5-carboxyluracil, but not 5-hydroxymethyluracil. Additionally, with the support of computational modeling, we revealed that proton affinity and acidity of the modified nucleobases govern the fragmentation of ODNs containing the alkylated and oxidized thymidine derivatives, respectively. These results provided important insights into the effects of thymine modifications on ODN fragmentation.

Original languageEnglish (US)
Pages (from-to)1167-1176
Number of pages10
JournalJournal of the American Society for Mass Spectrometry
Volume25
Issue number7
DOIs
StatePublished - Jul 2014

Keywords

  • DNA alkylation
  • DNA oxidation
  • Fragmentation of oligodeoxynucleotides
  • Gas phase acidity
  • Proton affinity

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