Guo Xiurong, Ingale Sachin A, Yang Haozhe, He Yang, Seela Frank
Precision Medicine Research Laboratory, West China Hospital, West China School of Medicine, Sichuan University, 610041 Chengdu, People's Republic of China and Laboratory of Bioorganic Chemistry and Chemical Biology, Center for Nanotechnology, Heisenbergstrasse 11, 48149 Münster, Germany.
Laboratory of Bioorganic Chemistry and Chemical Biology, Center for Nanotechnology, Heisenbergstrasse 11, 48149 Münster, Germany and Laboratorium für Organische und Bioorganische Chemie, Institut für Chemie neuer Materialien, Universität Osnabrück, Barbarastrasse 7, 49069 Osnabrück, Germany.
Org Biomol Chem. 2017 Jan 25;15(4):870-883. doi: 10.1039/c6ob02560a.
The stability of the mercury ion mediated dU-Hg-dU pair depends on substituents introduced at the 5-position of the pyrimidine moiety. To this end, a series of oligonucleotides were synthesized with dU modification in central position. Common and new phosphoramidites were utilized. Hybridization experiments provided 12-mer duplexes with non-canonical "dU-dU" pairs. In most cases Hg stabilizes duplexes by metal ion mediated base pair formation identified by higher duplex melting. Among the three types of dU derivatives incorporated in duplex DNA those with small aliphatic side chains have only a minor impact on the stability of the mercury-mediated base pair, while those with a triple bond in the side chain show hysteresis during duplex heating and cooling cycle implying triple bond interaction with mercury ions. Formation of metal ion mediated base pairs is blocked by space occupying aromatic side chains by side chain-helix stacking interactions. These interactions are too strong to permit mercury ion mediated base pair formation and drive the uridine N(3) acceptor atoms in an unfavorable pairing position.
汞离子介导的dU-Hg-dU碱基对的稳定性取决于嘧啶部分5位引入的取代基。为此，合成了一系列在中心位置进行dU修饰的寡核苷酸。使用了常见的和新型亚磷酰胺。杂交实验提供了具有非经典“dU-dU”碱基对的12聚体双链体。在大多数情况下，汞通过金属离子介导的碱基对形成使双链体稳定，这通过较高的双链体解链温度得以确定。在双链DNA中掺入的三种类型的dU衍生物中，具有小脂肪族侧链的那些对汞介导的碱基对稳定性影响较小，而侧链中有三键的那些在双链体加热和冷却循环中表现出滞后现象，这意味着三键与汞离子相互作用。金属离子介导的碱基对的形成被占据空间的芳香族侧链通过侧链-螺旋堆积相互作用所阻断。这些相互作用太强，以至于无法形成汞离子介导的碱基对，并将尿苷N(3)受体原子驱动到不利的配对位置。
