Oligonucleotide probes containing pyrimidine analogs reveal diminished hydrogen bonding capacity of the DNA adduct O⁶-methyl-G in DNA duplexes

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• 作者：Todor Angelov ; Heidi A. Dahlmann ; Shana J. Sturla
• 关键词：DNA adduct ; Oligonucleotide binding ; Nucleoside analog
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2013
• 出版时间：15 October, 2013
• 年：2013
• 卷：21
• 期：20
• 页码：6212-6216
• 全文大小：640 K

文摘

Oligonucleotide hybridization probes containing nucleoside analogs offer a potential strategy for binding specific DNA sequences that bear pro-mutagenic O⁶-G alkylation adducts. To optimize O⁶-Me-G-targeting probes, an understanding of how base pairs with O⁶-Me-G are stabilized is needed. In this study, we compared the ability of O⁶-Me-G and G to hydrogen bond with three pyrimidine-like nucleobases (Z, 4-thio-U, and 3-deaza-C) bearing varied hydrogen bond donor and acceptor groups. We found that duplexes containing the pyrimidine analog nucleoside:G pairs were more thermodynamically stable than those containing pyrimidine analog nucleoside:O⁶-alkyl-G pairs. Thus, hydrogen bonding alone was not sufficient to impart selectivity to probes that target O⁶-G alkylation adducts in DNA.