A Hitchhiker's Guide to Click-Chemistry with Nucleic Acids

Click chemistry is an immensely powerful technique for the fast and efficient covalent conjugation of molecular entities. Its broad scope has positively impacted on multiple scientific disciplines, and its implementation within the nucleic acid field has enabled researchers to generate a wide variety of tools with application in biology, biochemistry, and biotechnology. Azide-alkyne cycloadditions (AAC) are still the leading technology among click reactions due to the facile modification and incorporation of azide and alkyne groups within biological scaffolds. Application of AAC chemistry to nucleic acids allows labeling, ligation, and cyclization of oligonucleotides efficiently and cost-effectively relative to previously used chemical and enzymatic techniques. In this review, we provide a guide to inexperienced and knowledgeable researchers approaching the field of click chemistry with nucleic acids. We discuss in detail the chemistry, the available modified-nucleosides, and applications of AAC reactions in nucleic acid chemistry and provide a critical view of the advantages, limitations, and open-questions within the field.

Automated summary

Click chemistry, particularly azide-alkyne cycloadditions, is a powerful technique for the covalent conjugation of molecular entities. Its application in nucleic acid chemistry allows efficient and cost-effective labeling, ligation, and cyclization of oligonucleotides compared to traditional techniques. This review provides a guide to researchers approaching the field, discussing the chemistry and applications of AAC reactions in nucleic acids.