CHAPTER 5: Click Chemistry – a Versatile Method for Nucleic Acid Labelling, Cyclisation and Ligation

The copper-catalysed [3+2] alkyne azide cycloaddition reaction (the CuAAC reaction) is the classic example of ‘click’ chemistry, a relatively new concept that has been influential in many areas of science. It is used in the nucleic acid field for DNA cross-linking, oligonucleotide ligation and cyclisation, DNA and RNA labelling, attaching DNA to surfaces, producing modified nucleobases and backbones, synthesising ribozymes and monitoring nucleic acid biosynthesis. More recently a related click reaction, the ring strain-promoted azide–alkyne [3+2] cycloaddition (SPAAC) reaction has been used successfully in DNA strand ligation and labelling. This does not require copper catalysis, and therefore has many potential uses in vivo. In this review we discuss recent developments in nucleic acid click chemistry and their applications in biology, biotechnology and nanotechnology.