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Disparate proteome reactivity profiles of carbon electrophiles

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Abstract

Insights into the proteome reactivity of electrophiles are crucial for designing activity-based probes for enzymes lacking cognate affinity labels. Here, we show that different classes of carbon electrophiles exhibit markedly distinct amino acid labeling profiles in proteomes, ranging from selective reactivity with cysteine to adducts with several amino acids. These data specify electrophilic chemotypes with restricted and permissive reactivity profiles to guide the design of next-generation functional proteomics probes.

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Figure 1: Proteome and solution reactivities of carbon electrophile probes.
Figure 2: Labeling of ALDH and the CLIC protein family with carbon electrophile probes.

Change history

  • 29 May 2008

    In the version of this article initially published online, the two labels in Figure 2c that read 'CLIC4(C35C)' are incorrect. The correct labels should read 'CLIC4(C35S)'. The error has been corrected for all versions of the article.

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Acknowledgements

This work was supported by the US National Institutes of Health (CA087660) and the Skaggs Institute for Chemical Biology.

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E.W. and B.F.C. conceived and designed the experiments. E.W. carried out the experiments. E.W., G.M.S. and B.F.C. analyzed the experimental data. The manuscript was written by E.W. and B.F.C.

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Correspondence to Benjamin F Cravatt.

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Supplementary Figures 1–3, Supplementary Tables 1–5 and Supplementary Methods (PDF 513 kb)

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Weerapana, E., Simon, G. & Cravatt, B. Disparate proteome reactivity profiles of carbon electrophiles. Nat Chem Biol 4, 405–407 (2008). https://doi.org/10.1038/nchembio.91

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