TY - JOUR
T1 - Synthesis of DNA oligodeoxynucleotides containing site-specific 1,3-butadiene- deoxyadenosine lesions
AU - Wickramaratne, Susith
AU - Seiler, Christopher L.
AU - Tretyakova, Natalia Y.
N1 - Publisher Copyright:
© 2015 by John Wiley & Sons, Inc.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - 1,3-butadiene-induced DNA adducts
KW - Adenine
KW - Post-oligomerization synthesis
KW - Site- and stereospecific oligodeoxynucleotides
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U2 - 10.1002/0471142700.nc0461s61
DO - 10.1002/0471142700.nc0461s61
M3 - Article
C2 - 26344227
AN - SCOPUS:84949231998
SN - 1934-9270
VL - 2015
SP - 4.61.1-4.61.22
JO - Current protocols in nucleic acid chemistry
JF - Current protocols in nucleic acid chemistry
ER -