Click Nucleic Acid Ligation

A. H. El-Sagheer and T. Brown. Nucleic Acid Therapeutics (formerly Oligonucleotides) 21, A6, 2011.


Click DNA ligation is a remarkably efficient method of joining together DNA and RNA strands. It utilizes the copper-catalyzed azide-alkyne cycloaddition (CuAAC reaction). The chemistry has been optimized for the synthesis of cyclic oligonucleotides, oligonucleotide catenanes, very stable cyclic mini-duplexes, duplexes that are linked across the major groove, covalently fixed DNA nanoconstructs and large RNA constructs. The method produces an unnatural DNA backbone that can be varied by changing the participating alkyne and azide. Careful design produces a linkage that can be read through by thermostable DNA polymerases during PCR. This has potential applications in nanotechnology, gene synthesis and genetic analysis.