Synthesis and Characterization of Nucleosides and Oligonucleotides Bearing Adducts of Butadiene Epoxides on Adenine N6 and Guanine N2

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• 作者：Lubomir V. Nechev ; Mingzhu Zhang ; Dimitrios Tsarouhtsis ; Pamela J. Tamura ; Amanda S. Wilkinson ; Constance M. Harris ; and Thomas M. Harris
• 刊名：Chemical Research in Toxicology
• 出版年：2001
• 出版时间：April 2001
• 年：2001
• 卷：14
• 期：4
• 页码：379 - 388
• 全文大小：143K
• 年卷期：v.14,no.4(April 2001)
• ISSN：1520-5010

文摘

Butadiene is a major industrial chemical whose genotoxic effects are attributed to the reactionof its oxidized metabolites, butadiene monoepoxide (BDO) and butadiene diepoxide (BDO2),with DNA. Nucleosides and oligonucleotides containing regio- and stereochemically specificadducts of BDO and the BDO2-related compound, butene 3,4-diol 1,2-epoxide (BDE), on guanine[(2R)- and (2S)-N²-(1-hydroxy-3-buten-2-yl) and (2R,3R)- and (2S,3S)-N²-(2,3,4-trihydroxybut-1-yl), respectively] and on adenine [(2R)- and (2S)-N⁶-(1-hydroxy-3-buten-2-yl) and (2R,3R)-and (2S,3S)-N⁶-(2,3,4-trihydroxybut-1-yl), respectively] have been prepared by nonbiomimeticroutes. For guanine adducts, 2-fluoro-O⁶-(trimethylsilylethyl)-2'-deoxyinosine was treated with(2R)- and (2S)-2-amino-3-buten-1-ol to give the BDO adducts and with (2R,3R)- and (2S,3S)-1-amino-2,3,4-butanetriol to produce the BDE adducts; the adducted oligonucleotides wereprepared from 11-mer oligonucleotides containing the halopurine. Adenine adducts wereprepared in a similar fashion using 6-chloropurine 2'-deoxyriboside as the reactive purinecomponent.