Activity‐Based Probes Developed by Applying a Sequential Dehydroalanine Formation Strategy to Expressed Proteins Reveal a Potential α‐Globin‐Modulating Deubiquitinase. (14th April 2018)

• Record Type: Journal Article
• Authors: Meledin, Roman; Mali, Sachitanand M.; Kleifeld, Oded; Brik, Ashraf
• Is Part Of: Angewandte Chemie. Volume 130:Number 20(2018)
• Page Start: 5747
• Page End: 5751
• Publication Date: 2018-04-14
• Subjects: Aktivitätsbasierte Sonden -- Chemische Proteomik -- Dehydroalanin -- Proteinmodifikationen -- Ubiquitin; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201800032
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: 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 α‐globin probe, which was used for the enrichment and proteomic identification of α‐globin‐modulating deubiquitinases. We found USP15 as a potential deubiquitinase for the modulation of α‐globin, an excess of which aggravates β‐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.