Analysis and Optimization of Copper-Catalyzed Azide–Alkyne Cycloaddition for Bioconjugation

Authors

  • Vu Hong,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA), Fax: (+1) 858-784-8850
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  • Stanislav I. Presolski,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA), Fax: (+1) 858-784-8850
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  • Celia Ma,

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA), Fax: (+1) 858-784-8850
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  • M. G. Finn Prof.

    1. Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA), Fax: (+1) 858-784-8850
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  • This work was supported by The Skaggs Institue for Chemical Biology, Pfizer, Inc., and the NIH (RR021886). We are grateful to Matthias Park for assistance with the synthesis of 3.

Abstract

original image

How to click with biomolecules: Copper-catalyzed azide–alkyne cycloaddition has been optimized for use with biological molecules. The key development is the addition of two reagents that allow ascorbate to be used as reducing agent whilst eliminating problems caused by copper ascorbate side reactions. The result is a robust, rapid, and convenient procedure for the modification of proteins, DNA, RNA, and other biomolecules (see scheme).

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