| Autor: |
Robin Ramos, Anthi Karaiskou, Candice Botuha, Michaël Trichet, Florent Dingli, Jérémy Forté, France Lam, Alexis Canette, Chloé Chaumeton, Murielle Salome, Thomas Chenuel, Céline Bergonzi, Philippe Meyer, Sylvain Bohic, Damarys Loew, Michèle Salmain, Joëlle Sobczak-Thépot |
| Rok vydání: |
2023 |
| Popis: |
Identification of intracellular targets of anticancer drug candidates provides key information on their mechanism of action. Exploiting the ability of the anticancer (C^N)-chelated half-sandwich iridium(III) complexes to covalently bind proteins, click chemistry with a bioorthogonal azido probe was used to localize a phenyloxazoline-chelated iridium complex within cells and profile its interactome at the proteome-wide scale. Proteins involved in protein folding and actin cytoskeleton regulation were identified as high affinity targets. Upon iridium complex treatment, HSP90 folding activity was inhibitedin vitroand major cytoskeleton disorganization was observed. We used a wide array of imaging and biochemical methods to validate selected targets and obtain a multiscale overview of the effects of this complex on live human cells. We demonstrate that it behaves as a dual agent, inducing both electrophilic and oxidative stresses in cells that account for its cytotoxicity. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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