Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 57, Issue 20, Pages 5645-5649Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201800032
Keywords
activity-based probes; chemical proteomics; dehydroalanine; protein modifications; ubiquitin
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Funding
- Israel Science Foundation
- Taub Foundation
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We report a general and novel semisynthetic strategy for the preparation of ubiquitinated protein-activity-based probes on the basis of sequential dehydroalanine formation on expressed proteins. We applied this approach to construct a physiologically and therapeutically relevant ubiquitinated alpha-globin probe, which was used for the enrichment and proteomic identification of alpha-globin-modulating deubiquitinases. We found USP15 as a potential deubiquitinase for the modulation of alpha-globin, an excess of which aggravates beta-thalassemia symptoms. This development opens new opportunities for activity-based-probe design to shed light on the important aspects underlying ubiquitination and deubiquitination in health and disease.
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