Organic and Biomimetic Chemistry Research Group, Ghent University, Krijgslaan 281 S4, B-9000 Ghent, Belgium.
Organic and Biomimetic Chemistry Research Group, Ghent University, Krijgslaan 281 S4, B-9000 Ghent, Belgium.
Methods. 2023 Oct;218:189-197. doi: 10.1016/j.ymeth.2023.08.011. Epub 2023 Aug 18.
Oligonucleotides (ODNs) find applications as diagnostic and therapeutic tools due to their unique ability to interact, thanks to Watson-Crick base pairing, with a specific DNA or RNA target strand. Although most of the tools available today rely on mere hydrogen bond formation, chemical modifications to enable covalent interstrand-crosslinking (ICL) have been reported, and are gaining a place under the spotlight as they potentially offer a series of advantages over the state of the art, including a higher potency and selectivity. This methodological paper focuses on the use of a pro-reactive furan moiety and its subsequent oxidation for applications in ODN targeting. The design of effective capture and targeting probes to ensure high ICL yields is discussed and the mechanisms underlying the (photo)chemical oxidation of furan are explained. Furthermore, examples of furan-containing DNAs designed for different applications, including DNA-DNA or DNA-RNA ICL and DNA-peptide/protein targeting, are provided. The paper highlights the advantages of using different oxidative chemical triggers, such as N-bromosuccinimide or singlet oxygen, to offer additional selectivity control over the ICL reaction.
寡核苷酸 (ODNs) 由于其独特的能力，可以通过 Watson-Crick 碱基配对与特定的 DNA 或 RNA 靶链相互作用，因此被用作诊断和治疗工具。尽管当今大多数可用的工具仅依赖于氢键的形成，但已报道了能够实现共价链间交联 (ICL) 的化学修饰，并且由于它们相对于现有技术具有一系列优势，包括更高的效力和选择性，因此越来越受到关注。本方法学论文重点介绍了使用反应性呋喃部分及其随后的氧化在 ODN 靶向中的应用。讨论了设计有效的捕获和靶向探针以确保高 ICL 产率的方法，并解释了呋喃（光）化学氧化的机制。此外，还提供了设计用于不同应用的含呋喃 DNA 的示例，包括 DNA-DNA 或 DNA-RNA ICL 和 DNA-肽/蛋白质靶向。本文强调了使用不同氧化化学触发剂（如 N-溴代丁二酰亚胺或单线态氧）的优势，为 ICL 反应提供了额外的选择性控制。
