Total Synthesis, Mass Spectrometric Sequencing, and Stabilities of Oligonucleotide Duplexes with Singletrans-anti-BPDE-N6-dA Lesions in theN-rascodon 61 and Other Sequence Contexts

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 10S (+)-trans-lesions are consistently lower than those of duplexes containing the stereoisomeric 10R (-)-trans adducts. In contrast, similar duplexes, but with fjord region BcPhDE-N 6-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).

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