Synthesis of DNA Oligodeoxynucleotides Containing Site-Specific 1,3-Butadiene-Deoxyadenosine Lesions.
Post-oligomerization synthesis is a useful technique for preparing site-specifically modified DNA oligomers. This approach involves site-specific incorporation of inherently reactive halogenated nucleobases into DNA strands using standard solid-phase synthesis, followed by post-oligomerization nucleophilic aromatic substitution (SNAr) reactions with carcinogen-derived synthons. In these reactions, the inherent reactivities of DNA and carcinogen-derived species are reversed: the modified DNA nucleobase acts as an electrophile, while the carcinogen-derived species acts as a nucleophile. In the present protocol, we describe the use of the post-oligomerization approach to prepare DNA strands containing site- and stereospecific N6-adenine and N1,N6-adenine adducts induced by epoxide metabolites of the known human and animal carcinogen 1,3-butadiene (BD). The resulting oligomers containing site-specific, structurally defined DNA adducts can be used in structural and biological studies to reveal the roles of specific BD adducts in carcinogenesis and mutagenesis.
Department of Medicinal Chemistry and the Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
Susith
S
Wickramaratne
Department of Medicinal Chemistry and the Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
Christopher L
CL
Seiler
Department of Medicinal Chemistry and the Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
Natalia Y
NY
Tretyakova
D000225:Adenine / Q000737:chemistry; D002070:Butadienes / Q000737:chemistry; D018736:DNA Adducts / Q000737:chemistry*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*
D002070:Butadienes; D018736:DNA Adducts; D009838:Oligodeoxyribonucleotides; D000225:Adenine; C031763:1,3-butadiene
1,3-butadiene-induced DNA adducts; adenine; post-oligomerization synthesis; site- and stereospecific oligodeoxynucleotides