Cycloaddition reactions for site-specific or global modification of nucleic acids have enabled the preparation of a plethora of previously inaccessible DNA and RNA constructs for structural and functional studies on naturally occurring nucleic acids, the assembly of nucleic acid nanostructures, therapeutic applications, and recently, the development of novel aptamers. In this chapter, recent progress in nucleic acid functionalization via a range of different cycloaddition (click) chemistries is presented. At first, cycloaddition/click chemistries already used for modifying nucleic acids are summarized, ranging from the well-established copper(I)-catalyzed alkyne-azide cycloaddition reaction to copper free methods, such as the strain-promoted azide-alkyne cycloaddition, tetrazole-based photoclick chemistry and the inverse electron demand Diels-Alder cycloaddition reaction between strained alkenes and tetrazine derivatives. The subsequent sections contain selected applications of nucleic acid functionalization via click chemistry; in particular, site-specific enzymatic labeling in vitro, either via DNA and RNA recognizing enzymes or by introducing unnatural base pairs modified for click reactions. Further sections report recent progress in metabolic labeling and fluorescent detection of DNA and RNA synthesis in vivo, click nucleic acid ligation, click chemistry in nanostructure assembly and click-SELEX as a novel method for the selection of aptamers.

中文翻译：

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研究核酸的环加成物。

用于核酸的位点特异性或整体修饰的环加成反应使得能够制备大量以前无法获得的DNA和RNA构建体，用于对天然存在的核酸进行结构和功能研究，核酸纳米结构的组装，治疗应用，以及最近，新型适体的发展。在本章中，介绍了通过一系列不同的环加成（点击）化学方法在核酸功能化方面的最新进展。首先，概述了已经用于修饰核酸的环加成/点击化学，从公认的铜（I）催化的炔-叠氮化物环加成反应到无铜方法，例如由应变促进的叠氮化物-炔环加成，四唑基光点击化学和逆烯烃需求Diels-Alder环加成反应在应变烯烃和四嗪衍生物之间。随后的部分包含通过点击化学进行核酸功能化的选定应用；特别是通过DNA和RNA识别酶或通过引入针对点击反应修饰的非天然碱基对，在体外进行位点特异性酶标记。进一步的部分报道了在体内体内DNA和RNA合成的代谢标记和荧光检测，点击核酸连接，纳米结构组装中的点击化学以及点击-SELEX作为选择适体的新方法方面的最新进展。随后的部分包含通过点击化学进行核酸功能化的选定应用；特别是通过DNA和RNA识别酶或通过引入针对点击反应修饰的非天然碱基对，在体外进行位点特异性酶标记。进一步的部分报道了在体内体内DNA和RNA合成的代谢标记和荧光检测，点击核酸连接，纳米结构组装中的点击化学以及点击-SELEX作为选择适体的新方法方面的最新进展。随后的部分包含通过点击化学进行核酸功能化的选定应用；特别是通过DNA和RNA识别酶或通过引入针对点击反应修饰的非天然碱基对，在体外进行位点特异性酶标记。进一步的部分报道了在体内体内DNA和RNA合成的代谢标记和荧光检测，点击核酸连接，纳米结构组装中的点击化学以及点击-SELEX作为选择适体的新方法方面的最新进展。