Fast, Cell-Compatible Click Chemistry with Copper-Chelating Azides for Biomolecular Labeling


  • We thank Carolyn Kwa, Daniel Liu, and Ken Loh for assistance with neuron culture, Jennifer Yao for LplA enzymes, and Peng Zou for critical reading of the manuscript. Prof. M. G. Finn (Scripps) provided the initial batch of THPTA ligand. Funding was provided by the NIH (R01 GM072670), the Dreyfus Foundation, and the American Chemical Society. C.U. was supported by the C.P. Chu and Y. Lai summer graduate fellowship (MIT).


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Bring your own copper: Copper-chelating azides undergo much faster click reactions (CuAAC) than nonchelating azides under a variety of biocompatible conditions. This kinetic enhancement allows site-specific protein labeling to be performed on the surface of living cells with only 10–40 μM CuI/CuII (see scheme). Detection sensitivity was also increased for CuAAC detection of alkyne-modified proteins and RNA.