Abstract
The 2022 Nobel Prize in Chemistry was awarded to Professors K. Barry Sharpless, Morten Meldal and Carolyn Bertozzi for their pioneering roles in the advent of click chemistry. Sharpless and Meldal worked to develop the canonical click reaction—the copper-catalyzed azide–alkyne cycloaddition—while Bertozzi opened new frontiers with the creation of the bioorthogonal strain-promoted azide–alkyne cycloaddition. These two reactions have revolutionized chemical and biological science by facilitating selective, high yielding, rapid and clean ligations and by providing unprecedented ways to manipulate living systems. Click chemistry has affected every aspect of chemistry and chemical biology, but few disciplines have been impacted as much as radiopharmaceutical chemistry. The importance of speed and selectivity in radiochemistry make it an almost tailor-made application of click chemistry. In this Perspective, we discuss the ways in which the copper-catalyzed azide–alkyne cycloaddition, the strain-promoted azide–alkyne cycloaddition and a handful of ‘next-generation’ click reactions have transformed radiopharmaceutical chemistry, both as tools for more efficient radiosyntheses and as linchpins of technologies that have the potential to improve nuclear medicine.
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Acknowledgements
The authors are grateful to the National Institutes of Health (NIH) (R35CA232130 to J.S.L.; R01CA204167 and U01CA221046 to J.S.L. and B.M.Z.; R01CA240963 and R01CA244327 to B.M.Z.) and the Tow Foundation (D.B.) for their generous support.
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B.M.Z. and J.S.L. hold intellectual property related to the application of click chemistry to radiopharmaceutical chemistry. D.B. and S.M.S. declare no competing interests.
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Bauer, D., Sarrett, S.M., Lewis, J.S. et al. Click chemistry: a transformative technology in nuclear medicine. Nat Protoc 18, 1659–1668 (2023). https://doi.org/10.1038/s41596-023-00825-8
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DOI: https://doi.org/10.1038/s41596-023-00825-8
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