Targeting Gαi/s Proteins with Peptidyl Nucleotide Exchange Modulators
| Autor: | Britta Nubbemeyer, Ajay Abisheck Paul George, Toni Kühl, Anna Pepanian, Maximilian Steve Beck, Rahma Maghraby, Maryam Shetab Boushehri, Maximilian Muehlhaupt, Eva Marie Pfeil, Suvi Katariina Annala, Hermann Ammer, Diana Imhof, Dehua Pei |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | ACS Chemical Biology. 17:463-473 |
| ISSN: | 1554-8937 1554-8929 |
| Popis: | Chemical probes that specifically modulate the activity of heterotrimeric G proteins provide excellent tools for investigating G protein-mediated cell signaling. Herein, we report a family of selective peptidyl Gαi/s modulators derived from peptide library screening and optimization. Conjugation to a cell-penetrating peptide rendered the peptides cell-permeable and biologically active in cell-based assays. The peptides exhibit potent guanine-nucleotide exchange modulator-like activity toward Gαi and Gαs. Molecular docking and dynamic simulations revealed the molecular basis of the protein-ligand interactions and their effects on GDP binding. This study demonstrates the feasibility of developing direct Gαi/s modulators and provides a novel chemical probe for investigating cell signaling through GPCRs/G proteins. |
| Databáze: | OpenAIRE |
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