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Developing Isoxazole as a Native Photo‐Cross‐Linker for Photoaffinity Labeling and Chemoproteomics
- Source :
- Angewandte Chemie. 134
- Publication Year :
- 2022
- Publisher :
- Wiley, 2022.
-
Abstract
- Photoaffinity labeling is a powerful technique to interrogate drug-protein interactions in native cellular environments. Photo-cross-linkers are instrumental for this technique. However, the introduction of unnatural photo-cross-linkers may significantly reduce the bioactivity of the drug, thus impairing the chemoproteomic outcomes. Herein, we developed a common pharmacophore, isoxazole, into a natively embedded photo-cross-linker for chemoproteomics, which minimally perturbs the drug structure. The photo-cross-linking reactions of the isoxazole were thoroughly investigated for the first time. Functionalized isoxazoles were then designed and applied to protein labeling, demonstrating the superior photo-cross-linking efficiency. Subsequently, two isoxazole-based drugs, Danazol and Luminespib, were employed in chemoproteomic studies, revealing their potential cellular targets. These results provide valuable strategies for future chemoproteomic study and drug development.
Details
- ISSN :
- 15213757 and 00448249
- Volume :
- 134
- Database :
- OpenAIRE
- Journal :
- Angewandte Chemie
- Accession number :
- edsair.doi.dedup.....1e2ad37db181d8195ccc9d18f3a86f72