Bioconjugation by copper(I)-catalyzed azide-alkyne [3 + 2] cycloaddition

J Am Chem Soc. 2003 Mar 19;125(11):3192-3. doi: 10.1021/ja021381e.


The copper-catalyzed cycloaddition reaction between azides and alkynes functions efficiently in aqueous solution in the presence of a tris(triazolyl)amine ligand. The process has been employed to make rapid and reliable covalent connections to micromolar concentrations of protein decorated with either of the reactive moieties. The chelating ligand plays a crucial role in stabilizing the Cu(I) oxidation state and protecting the protein from Cu(triazole)-induced denaturation. Because the azide and alkyne groups themselves are unreactive with protein residues or other biomolecules, their ligation is of potential utility as a general bioconjugation method.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkynes / chemistry*
  • Azides / chemistry*
  • Azoles / chemical synthesis*
  • Capsid Proteins / chemistry*
  • Catalysis
  • Comovirus / chemistry*
  • Copper / chemistry*
  • Hydrogen-Ion Concentration


  • Alkynes
  • Azides
  • Azoles
  • Capsid Proteins
  • Copper