Total Synthesis, Mass Spectrometric Sequencing, and Stabilities of Oligonucleotide Duplexes with Single trans-anti-BPDE-N6-dA Lesions in the N-ras codon 61 and Other Sequence Contexts

Jacek Krzeminski, Jinsong Ni, Ping Zhuang, Natalia Luneva, Shantu Amin, Nicholas E. Geacintov

Research output: Contribution to journalArticlepeer-review

Abstract

Three different oligonucleotides (one of them comprising a portion of the N-ras protooncogene) with single bay region anti-BPDE-modified adenine residues (anti-BPDE = 7r,8t-dihydroxy-t9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene) were prepared by total synthesis methods, characterized, and sequenced by electrospray tandem mass spectrometry techniques. While all of the BPDE-modified duplexes are destabilized relative to the unmodified double-stranded oligonucleotides, the thermodynamic stabilities of duplexes containing 105 (+)-trans-lesions are consistently lower than those of duplexes containing the stereoisomeric 10R (-)-trans adducts. In contrast, similar duplexes, but with fjord region BcPhDE-N6-dA adducts are not thermodynamically destabilized by these bulky lesions (anti-BcPhDE: 4r,3t-dihydroxy-t1,2-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene).

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalPolycyclic Aromatic Compounds
Volume17
Issue number1-4
DOIs
StatePublished - 1999

Keywords

  • Benzo[a]pyrene diol epoxide
  • Benzo[c]phenanthrene diol epoxide
  • DNA adducts
  • Deoxyadenosine lesions
  • Stereochemistry
  • Thermodynamic stability

ASJC Scopus subject areas

  • Polymers and Plastics
  • Organic Chemistry
  • Materials Chemistry

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