Over the past 20 years,great efforts have been invested in developing site-specific approaches to protein modification to dissect protein functions directly and accurately.Here,we report a proximitytriggered group tra...Over the past 20 years,great efforts have been invested in developing site-specific approaches to protein modification to dissect protein functions directly and accurately.Here,we report a proximitytriggered group transfer strategy from a sulfonium warhead to a Cysteine(Cys)residue of the target protein.With a guiding ligand,cargoes could be transferred selectively from a sulfonium center onto the Cys residue in the vicinity of their binding interface.The successful thalidomide transfer of sulfonium 1-X could be applied intracellularly for epidermal growth factor receptor degradation,highlighting the potential of group transfer strategy as a suite of chemical biology studies,including cell imaging,protein profiling,and protein degradation by simply employing different transferrable groups.展开更多
基金Weare grateful for the financial support from the Natural Science Foundation of China(grant nos.21778009,21977010,and 22007033)National Key Research and Development Program“Synthetic Biology”Key Special Project of China(grant no.2018YFA0902504)+3 种基金China Postdoctoral Science Foundation(grant no.2021M690220)the Natural Science Foundation of Guangdong Province(grant nos.2020A1515010522,2020A1515010766,2019A1515110487,and 2019A151-5111184)the Foundation for Basic and Applied Research of Guangdong Province(grant no.2019A1515110489)and the Shenzhen Science and Technology Innovation Committee(grant nos.JCYJ20180507181527112,JCYJ-201805081522131455,and JCYJ20170817172023838).
文摘Over the past 20 years,great efforts have been invested in developing site-specific approaches to protein modification to dissect protein functions directly and accurately.Here,we report a proximitytriggered group transfer strategy from a sulfonium warhead to a Cysteine(Cys)residue of the target protein.With a guiding ligand,cargoes could be transferred selectively from a sulfonium center onto the Cys residue in the vicinity of their binding interface.The successful thalidomide transfer of sulfonium 1-X could be applied intracellularly for epidermal growth factor receptor degradation,highlighting the potential of group transfer strategy as a suite of chemical biology studies,including cell imaging,protein profiling,and protein degradation by simply employing different transferrable groups.
