Bioconjugation by copper(I)-catalyzed azide-alkyne [3 + 2] cycloaddition.
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.
Wang
Qian
Q
Departments of Chemistry and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Chan
Timothy R
TR
Hilgraf
Robert
R
Fokin
Valery V
VV
Sharpless
K Barry
KB
Finn
M G
MG
D000480:Alkynes / Q000737:chemistry*; D001386:Azides / Q000737:chemistry*; D001393:Azoles / Q000138:chemical synthesis*; D036022:Capsid Proteins / Q000737:chemistry*; D002384:Catalysis; D017798:Comovirus / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration
D000480:Alkynes; D001386:Azides; D001393:Azoles; D036022:Capsid Proteins; D003300:Copper