Synthesis and Characterization of Oligonucleotides Containing 5,8-Cyclopurine 2-Deoxyribonucleosides: (5R)-5,8-Cyclo-2-deoxyadenosine, (5S)-5,8-Cyclo-2-deoxyguanosine, and (5R)-5,8-Cyclo-2-deoxyguanosine

Radiation-induced degradation of purine and pyrimidine nucleosides gave rise to carbonbridged cyclocompounds. Such cyclonucleosides represent a class of tandem lesions in which modification of both the base and 2-deoxyribose has occurred. A solid-phase synthetic method was designed for the incorporation of both 5ʹR and 5ʹS diastereoisomers of 5ʹ,8-cyclopurine 2ʹ-deoxyribonucleosides into oligodeoxynucleotides to facilitate the assessment of the biochemical and biophysical features of such lesions. We report the preparation of the phosphoramidite synthons of (5ʹR)-5ʹ,8-cyclo-2ʹ-deoxyadenosine (2), (5ʹS)-5ʹ,8-cyclo-2ʹ-deoxyguanosine (3), and (5ʹR)-5ʹ,8-cyclo-2ʹ-deoxyguanosine (4). Fully protected compounds 10, 18, and 25 were then inserted into several oligonucleotides by automated procedures. Analysis of modified DNA oligomers 26-31 by electrospray mass spectrometry and enzymatic digestions with exo- and endonucleases confirmed the base compositions and the integrity of free radical-induced tandem lesions 2-4 that were chemically inserted.