Bioconjugation by Copper(I)-Catalyzed Azide-Alkyne [3 + 2] Cycloaddition

• Published in: Journal of the American Chemical Society Vol. 125; no. 11; pp. 3192 - 3193
• Main Authors: Wang, Qian, Chan, Timothy R, Hilgraf, Robert, Fokin, Valery V, Sharpless, K. Barry, Finn, M. G
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 19-03-2003
• Subjects: Alkynes - chemistry; Azides - chemistry; Azoles - chemical synthesis; Biological and medical sciences; Capsid Proteins - chemistry; Catalysis; Chemistry; Comovirus - chemistry; Copper - chemistry; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; Hydrogen-Ion Concentration; Kinetics and mechanisms; Mechanisms. Catalysis. Electron transfer. Models; Molecular biophysics; Organic chemistry; Physical chemistry in biology; Reactivity and mechanisms; Mixed catalyst; Catalytic reaction; Comovirus; Acetylenic compound; Organic azide; Cowpea mosaic virus; Transition metal Compounds; Comoviridae; Experimental study; Biocatalyst; Dipolar cycloaddition; Virus; Kinetic parameter; Rate constant; Catalyst activity; Alkyne; Copper sulfate
• ISSN: 0002-7863; 1520-5126
• 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.