含位点特异性1,3 - 丁二烯 - 脱氧腺苷损伤的DNA寡脱氧核苷酸的合成
Synthesis of DNA Oligodeoxynucleotides Containing Site-Specific 1,3-Butadiene-Deoxyadenosine Lesions.
作者信息
Wickramaratne Susith, Seiler Christopher L, Tretyakova Natalia Y
机构信息
Department of Medicinal Chemistry and the Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
出版信息
Curr Protoc Nucleic Acid Chem. 2015 Jun 3;61:4.61.1-4.61.22. doi: 10.1002/0471142700.nc0461s61.
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.
寡聚后合成是制备位点特异性修饰的DNA寡聚物的一种有用技术。该方法包括使用标准固相合成将具有固有反应性的卤代核碱基位点特异性掺入DNA链中，随后进行与致癌物衍生合成子的寡聚后亲核芳香取代（SNAr）反应。在这些反应中，DNA和致癌物衍生物种的固有反应性发生了逆转：修饰的DNA核碱基充当亲电试剂，而致癌物衍生物种充当亲核试剂。在本方案中，我们描述了使用寡聚后方法制备含有由已知人类和动物致癌物1,3 - 丁二烯（BD）的环氧化物代谢物诱导的位点特异性和立体特异性N6 - 腺嘌呤和N1,N6 - 腺嘌呤加合物的DNA链。所得含有位点特异性、结构明确的DNA加合物的寡聚物可用于结构和生物学研究，以揭示特定BD加合物在致癌作用和诱变作用中的作用。
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