Department of Chemistry and Biochemistry, University of Bern, CH-3012, Bern, Switzerland.
Mass Spectrom Rev. 2016 Jul;35(4):483-523. doi: 10.1002/mas.21442. Epub 2014 Oct 6.
Nucleic acids play key roles in the storage and processing of genetic information, as well as in the regulation of cellular processes. Consequently, they represent attractive targets for drugs against gene-related diseases. On the other hand, synthetic oligonucleotide analogues have found application as chemotherapeutic agents targeting cellular DNA and RNA. The development of effective nucleic acid-based chemotherapeutic strategies requires adequate analytical techniques capable of providing detailed information about the nucleotide sequences, the presence of structural modifications, the formation of higher-order structures, as well as the interaction of nucleic acids with other cellular components and chemotherapeutic agents. Due to the impressive technical and methodological developments of the past years, tandem mass spectrometry has evolved to one of the most powerful tools supporting research related to nucleic acids. This review covers the literature of the past decade devoted to the tandem mass spectrometric investigation of nucleic acids, with the main focus on the fundamental mechanistic aspects governing the gas-phase dissociation of DNA, RNA, modified oligonucleotide analogues, and their adducts with metal ions. Additionally, recent findings on the elucidation of nucleic acid higher-order structures by tandem mass spectrometry are reviewed. © 2014 Wiley Periodicals, Inc., Mass Spec Rev 35:483-523, 2016.
核酸在遗传信息的存储和处理以及细胞过程的调节中起着关键作用。因此，它们是针对与基因相关疾病的药物的有吸引力的靶标。另一方面，合成寡核苷酸类似物已被用作针对细胞 DNA 和 RNA 的化学治疗剂。有效的基于核酸的化学治疗策略的发展需要适当的分析技术，这些技术能够提供有关核苷酸序列、结构修饰的存在、高级结构的形成以及核酸与其他细胞成分和化学治疗剂的相互作用的详细信息。由于过去几年令人印象深刻的技术和方法学发展，串联质谱已发展成为支持与核酸相关研究的最强大工具之一。本综述涵盖了过去十年中致力于串联质谱研究核酸的文献，主要重点是控制 DNA、RNA、修饰的寡核苷酸类似物及其与金属离子的加合物在气相中解离的基本机理方面。此外，还回顾了通过串联质谱阐明核酸高级结构的最新发现。©2014 年 Wiley 期刊，Inc.，质谱评论 35：483-523，2016 年。
