Discovery of a cell-active SuTEx ligand of prostaglandin reductase 2
| Autor: | Adam H. Libby, Ku-Lung Hsu, Emmanuel K. Toroitich, Anthony M. Ciancone, Skylar M Brodowski, Heung Sik Hahm |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cell
Prostaglandin Reductase Ligands Biochemistry Article law.invention chemistry.chemical_compound Structure-Activity Relationship law Drug Discovery medicine Humans Tyrosine Enzyme Inhibitors 15-Oxoprostaglandin 13-Reductase Molecular Biology Molecular Structure Sulfur Compounds Ligand Organic Chemistry Activity-based proteomics Biochemical Activity Triazoles Recombinant Proteins medicine.anatomical_structure HEK293 Cells chemistry Recombinant DNA Molecular Medicine Sulfur |
| Zdroj: | Chembiochem |
| Popis: | Sulfonyl-triazoles have emerged as a new reactive group for covalent modification of tyrosine sites on proteins through sulfur-triazole exchange (SuTEx) chemistry. The extent to which this sulfur electrophile can be tuned for developing ligands with cellular activity remains largely underexplored. Here, we performed fragment-based ligand discovery in live cells to identify SuTEx compounds capable of liganding tyrosine sites on diverse protein targets. We verified our quantitative chemical proteomic findings by demonstrating concentration-dependent activity of SuTEx ligands, but not inactive counterparts, against recombinant protein targets directly in live cells. Our structure-activity relationship studies identified the SuTEx ligand HHS-0701 as a cell-active inhibitor capable of blocking prostaglandin reductase 2 (PTGR2) biochemical activity. |
| Databáze: | OpenAIRE |
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