Department of Health Science and Technology, Institute of Food, Nutrition and Health, ETH Zurich, Schmelzbergstrasse 9, 8092 Zurich, Switzerland.
Bioorg Med Chem. 2013 Oct 15;21(20):6212-6. doi: 10.1016/j.bmc.2013.07.036. Epub 2013 Jul 26.
Oligonucleotide hybridization probes containing nucleoside analogs offer a potential strategy for binding specific DNA sequences that bear pro-mutagenic O(6)-G alkylation adducts. To optimize O(6)-Me-G-targeting probes, an understanding of how base pairs with O(6)-Me-G are stabilized is needed. In this study, we compared the ability of O(6)-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:O(6)-alkyl-G pairs. Thus, hydrogen bonding alone was not sufficient to impart selectivity to probes that target O(6)-G alkylation adducts in DNA.
寡核苷酸杂交探针中包含核苷类似物，为结合具有致突变 O(6)-G 烷基化加合物的特定 DNA 序列提供了一种潜在策略。为了优化针对 O(6)-Me-G 的探针，需要了解带有 O(6)-Me-G 的碱基对是如何稳定的。在这项研究中，我们比较了 O(6)-Me-G 和 G 与三个带有不同氢键供体和受体基团的嘧啶类似物核苷（Z、4-硫代-U 和 3-脱氮-C）形成氢键的能力。我们发现，含有嘧啶类似物核苷：G 对的双链体比含有嘧啶类似物核苷：O(6)-烷基-G 对的双链体热力学更稳定。因此，仅氢键不足以赋予针对 DNA 中 O(6)-G 烷基化加合物的探针选择性。
