Click Chemistry in Nucleic Acids

Copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction (known as Click Chemistry) has significantly impacted nucleic acid chemistry by providing a reliable and versatile method for modifying DNA and RNA. This modular reaction facilitates the efficient and selective formation of 1,2,3-triazole linkages between azide and alkyne functional groups, enabling the precise conjugation of nucleic acids with various molecular entities. CuAAC is instrumental in the synthesis of labeled oligonucleotides, bioconjugates, and nucleic acid-based probes, enhancing the development of diagnostic tools, therapeutic agents, and nanostructures. Its compatibility with aqueous conditions and tolerance for diverse functional groups make CuAAC ideal for applications in molecular biology and biotechnology. This chapter highlights the transformative role of CuAAC in nucleic acid chemistry, focusing on its applications in probing, imaging, and therapeutic developments, and underscoring its contribution to advancing nucleic acid research and biomedicine.