Click chemistry with copper – A biocompatible version

Click chemistry with copper – A biocompatible version

3:32 PM, 19th July 2011
Click chemistry with copper – A biocompatible version
Yi Liu, (right) a chemist with Berkeley Lab’s Molecular Foundry, along with Liana Klivansky and David Hanifi.

BERKELEY, US: Biomolecular imaging can reveal a great deal of information about the inner workings of cells and one of the most attractive targets for imaging are glycans - sugars that are ubiquitous to living organisms and abundant on cell surfaces. Imaging a glycan requires that it be tagged or labelled. One of the best techniques for doing this is a technique called click chemistry. Now, a variation of click chemistry has been introduced that retains the copper catalyst of the original reaction - along with its speed and specificity - but is safe for cells in vivo.

Researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab), in collaboration with researchers at the Albert Einstein College of Medicine at Yeshiva University in New York, have found a way to make copper-catalyzed click chemistry biocompatible. By adding a ligand that minimizes the toxicity of copper but still allows it to catalyze the click chemistry reaction, the researchers can safely use their reaction in living organisms. Compared to the copper-free click chemistry reaction, which can take up to an hour, the ligand-accelerated copper-catalyzed click chemistry reaction can achieve effective labelling within 3-5 minutes.

“The discovery of this new accelerating ligand for copper-catalyzed click chemistry should provide an effective complimentary tool to copper-free click chemistry,” said Yi Liu, a Chemist with Berkeley Lab’s Molecular Foundry and the co-leader of this research with Peng Wu, of the Albert Einstein College of Medicine.

The ligand-accelerated copper-catalyzed reaction was used to label glycans in recombinant glycoproteins, glycoproteins in cell lysates, glycoproteins on live cell surfaces and glycoconjugates in live zebrafish embryos.

“Based on our results,” said Peng Wu, “We believe that ligand-accelerated copper-catalyzed click chemistry represents a powerful and highly adaptive bioconjugation tool that holds great promise for further improvement with the discovery of more versatile catalyst systems.”

The Click chemistry technique proved valuable for attaching small molecular probes to various biomolecules in a test tube or on fixed cells, but it could not be used for biomolecule labelling in live cells or organisms because of the copper catalyst.

“Our bio-benign ligand-accelerated copper-catalyzed click chemistry reaction liberates bioconjugation from the limitation where ligations could only be accomplished with azide-tagged biomolecules,” Liu said. “Now terminal alkyne residues can also be incorporated into biomolecules and detected in vivo.”

The latest paper on this research appears in the journal Angewandte Chemie, titled “Raising the Efficacy of Bioorthogonal Click Reactions for Bioconjugation: A Comparative Study.” Co-authoring the paper with Liu and Wu were Christen Besanceney-Webler, Hao Jiang, Tianqing Zheng, Lei Feng, David Soriano del Amo, Wei Wang, Liana Klivansky and Florence Marlow.

This work was supported by a grant from the National Institutes of Health, and in part as a User Project at the Molecular Foundry, which is funded through DOE’s Office of Science.

© Berkeley Lab News

 

 

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