Total synthesis, mass spectrometric sequencing, and stabilities of oligonucleotide duplexes with single trans-anti-BPDE-N-6-dA lesions in the N-ras codon 61 and other sequence contexts

Three different oligonucleotides tone of them comprising a portion of the N -ras protooncogene) with single bay region anti-BPDE-modified adenine resid ues (anti-BPDE = 7r,8t-dihydroxy-t9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyr ene) 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-stran ded oligonucleotides, the thermodynamic stabilities of duplexes containing 10S (+)-trans-lesions are consistently lower than those of duplexes contain ing the stereoisomeric 10R (-)-trans adducts; In contrast, similar duplexes , but with fjord region BcPhDE-N-6-dA adducts are not thermodynamically des tabilized by these bulky lesions (anti-BcPhDE: 4r,3t-dihydroxy-t1,2epoxy-1, 2,3,4-tetrahydrobenzo [c]phenanthrene).