Developing Isoxazole as a Native Photo-Cross-Linker for Photoaffinity Labeling and Chemoproteomics
Research output: Journal Publications and Reviews (RGC: 21, 22, 62) › 21_Publication in refereed journal › peer-review
Author(s)
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Detail(s)
Original language | English |
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Article number | e202209947 |
Journal / Publication | Angewandte Chemie - International Edition |
Volume | 61 |
Issue number | 47 |
Online published | 23 Sep 2022 |
Publication status | Published - 21 Nov 2022 |
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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.
Research Area(s)
- Chemoproteomics, Drug Discovery, Isoxazole, Photo-Cross-Linker, Photoaffinity Labeling
Citation Format(s)
Developing Isoxazole as a Native Photo-Cross-Linker for Photoaffinity Labeling and Chemoproteomics. / Cheng, Ke; Qi, Junyang; Ren, Xiaojie et al.
In: Angewandte Chemie - International Edition, Vol. 61, No. 47, e202209947, 21.11.2022.Research output: Journal Publications and Reviews (RGC: 21, 22, 62) › 21_Publication in refereed journal › peer-review