"Click chemistry" usually refers to the reaction of an azide with an alkyne yielding 1,5-disubstituted 1,2,3-triazoles. Without additives, this reaction (Huisgen 1,3-dipolar cycloaddition) is relatively slow. However, in 2002 a copper(I)-catalyzed version was reported independently by Meldal and Sharpless. As under copper-catalysis the reaction proceeds quickly and selectively, Sharpless coined the term "click reaction". Another common name for the copper-catalyzed variant is CuAAC (Cu catalyzed alkyne azide cycloaddition).
- The reaction is fast and quantitative
- The reaction is irreversible
- The reaction is compatible with all functional groups present in natural peptides
- The reaction is compatible with water
- The reaction is pH insensitive (in the range of pH 4-11).
- The triazole moiety formed by the click reaction is similar in geometry and polarity to the amide bond
- The formed triazole is stable (e.g. to oxidation, hydrolysis, enzymatic degradation)
- Azides and alkynes are easy to introduce into peptides