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

被引：41

作者：

Meledin, Roman ^{[1
]}

Mali, Sachitanand M. ^{[1
]}

Kleifeld, Oded ^{[2
]}

Brik, Ashraf ^{[1
]}

机构：

[1] Technion Israel Inst Technol, Schulich Fac Chem, IL-3200008 Haifa, Israel

[2] Technion Israel Inst Technol, Fac Biol, IL-3200003 Haifa, Israel

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2018年 / 57卷 / 20期

基金：

以色列科学基金会;

关键词：

activity-based probes; chemical proteomics; dehydroalanine; protein modifications; ubiquitin; DEUBIQUITYLATING ENZYMES; DIUBIQUITIN PROBES; MASS-SPECTROMETRY; BETA-THALASSEMIA; QUALITY-CONTROL; PROTEOMICS; CYSTEINE; CHAINS; UBIQUITINATION; SPECIFICITY;

D O I：

10.1002/anie.201800032

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：5645 / 5649

页数：5

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