Global targeting of functional tyrosines using sulfur-triazole exchange chemistry
| Autor: | Jeffrey W. Brulet, Emmanuel K. Toroitich, Adam L. Borne, Ku-Lung Hsu, Adam H. Libby, Kun Yuan, Rebecca L. McCloud, Heung Sik Hahm, Anthony M. Ciancone, Timothy B. Ware |
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| Rok vydání: | 2019 |
| Předmět: |
Proteomics
Chemical biology Article 03 medical and health sciences Protein Domains Human proteome project Humans Phosphorylation Chemoselectivity Binding site Phosphotyrosine Molecular Biology 030304 developmental biology chemistry.chemical_classification 0303 health sciences Binding Sites Chemistry 030302 biochemistry & molecular biology Phosphoproteomics Fluorine Cell Biology Triazoles Sulfinic Acids Combinatorial chemistry Amino acid HEK293 Cells Glutathione S-Transferase pi A549 Cells Molecular Probes Proteome Tyrosine Protein Processing Post-Translational Sulfur |
| Zdroj: | Nature chemical biology |
| ISSN: | 1552-4469 1552-4450 |
| Popis: | Covalent probes serve as valuable tools for global investigation of protein function and ligand binding capacity. Despite efforts to expand coverage of residues available for chemical proteomics (e.g. cysteine and lysine), a large fraction of the proteome remains inaccessible with current activity-based probes. Here, we introduce sulfur-triazole exchange (SuTEx) chemistry as a tunable platform for developing covalent probes with broad applications for chemical proteomics. We show modifications to the triazole leaving group can furnish sulfonyl probes with ~5-fold enhanced chemoselectivity for tyrosines over other nucleophilic amino acids to investigate, for the first time, more than 10,000 tyrosine sites in lysates and live cells. We discover that tyrosines with enhanced nucleophilicity are enriched in enzymatic, protein-protein interaction, and nucleotide recognition domains. We apply SuTEx as a chemical phosphoproteomics strategy to monitor activation of phosphotyrosine sites. Collectively, we describe SuTEx as a biocompatible chemistry for chemical biology investigations of the human proteome. |
| Databáze: | OpenAIRE |
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