Synthesis and characterization of oligonucleotides containing 5',8-cyclopurine 2'-deoxyribonucleosides: (5'R)-5',8-cyclo-2'-deoxyadenosine, (5'S)-5',8-cyclo-2'-deoxyguanosine, and (5'R)-5',8-cyclo-2'-deoxyguanosine.
Radiation-induced degradation of purine and pyrimidine nucleosides gave rise to carbon-bridged 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 5'R and 5'S diastereoisomers of 5',8-cyclopurine 2'-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 (5'R)-5', 8-cyclo-2'-deoxyadenosine (2), (5'S)-5',8-cyclo-2'-deoxyguanosine (3), and (5'R)-5',8-cyclo-2'-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.
D000469:Alkaline Phosphatase; D002851:Chromatography, High Pressure Liquid; D003839:Deoxyadenosines / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification; D006868:Hydrolysis; D007202:Indicators and Reagents; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D010727:Phosphoric Diester Hydrolases; D015719:Single-Strand Specific DNA and RNA Endonucleases; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism