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Default Activity-Based Probes Developed by Applying Sequential Dehydroalanine Strategy on Expressed Proteins Reveal a Potential ?-globin Modulating Deubiquitinase

Activity-Based Probes Developed by Applying Sequential Dehydroalanine Strategy on Expressed Proteins Reveal a Potential ?-globin Modulating Deubiquitinase


We report a general and novel semisynthetic strategy for the preparation of ubiquitinated protein activity based probes applying sequential dehydroalanine formation on expressed proteins. We applied this approach to construct physiologically and therapeutically relevant ubiquitinated ?-globin probe, which was used for the enrichment and proteomic identification of ?-globin modulating deubiquitinases. We found USP15 as a potential deubiquitinase, modulating ?-globin, which excess aggravates beta-thalassemia symptoms. This development opens new opportunities for the activity based probe design to shed light on the important aspects underlining ubiquitination and deubiquitination in health and disease.

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