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Suzuki–Miyaura cross-coupling for chemoproteomic applications

preprint
submitted on 31.03.2020, 18:18 and posted on 01.04.2020, 13:31 by Jian Cao, Ernest Armenta, Lisa Boatner, Heta Desai, Neil Chan, Jose Castellon, Keriann Backus
Bioorthogonal chemistry is a mainstay of chemoproteomic sample preparation workflows. While numerous transformations are now available, chemoproteomic studies still rely overwhelmingly on copper-catalyzed azide –alkyne cycloaddition (CuAAC) or 'click' chemistry. Here we demonstrate that gel-based activity-based protein profiling (ABPP) and mass-spectrometry-based chemoproteomic profiling can be conducted using Suzuki–Miyaura cross-coupling. We identify reaction conditions that proceed in complex cell lysates and find that Suzuki –Miyaura cross-coupling and CuAAC yield comparable chemoproteomic coverage. Importantly, Suzuki–Miyaura is also compatible with chemoproteomic target deconvolution, as demonstrated using structurally matched probes tailored to react with the cysteine protease caspase-8. Uniquely enabled by the observed orthogonality of palladium-catalyzed cross-coupling and CuAAC, we combine both reactions to achieve dual protein labeling.

Funding

D19AP00041

History

Email Address of Submitting Author

kbackus@mednet.ucla.edu

Institution

UNIVERSITY OF CALIFORNIA LOS ANGELES

Country

United States

ORCID For Submitting Author

0000-0001-8541-1404

Declaration of Conflict of Interest

The authors declare no competing interests.

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