Activity-Based Probes Developed by Applying a Sequential Dehydroalanine Formation Strategy to Expressed Proteins Reveal a Potential α-Globin-Modulating Deubiquitinase

Roman Meledin, Sachitanand M. Mali, Oded Kleifeld, Ashraf Brik

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish
Pages (from-to)5645-5649
Number of pages5
JournalAngewandte Chemie - International Edition
Volume57
Issue number20
DOIs
StatePublished - 14 May 2018
Externally publishedYes

Keywords

  • activity-based probes
  • chemical proteomics
  • dehydroalanine
  • protein modifications
  • ubiquitin

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