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Peiwen Shi, Bruno N. Melillo, Matthew W. McHenry, Christina M. Camara et autres
No therapies directly block apoptosis in tissue injury or the many diseases driven by cell loss. The BCL-2 family protein BAX is a central mediator of this pathway and C126 resides within a key regulatory region where physiologic or pharmacologic ligands can …
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Jason E Tse, William R. Brothers, Rachel E. Hayward, Sabrina Barbas et autres
Chemical proteomics has identified covalent ligands targeting cysteine residues across many hundreds of human proteins. The functional effects of these liganding events, however, remain challenging to assign at scale. Here we describe ESCAPE (Endogenous Site-specific Competition Assays using Prime Editors), a platform …
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Minjin Yoo, Timothy B. Ware, Sebastian Moschen, Alex W. Reed et autres
Abstract Zymoseptoria (Z.) tritici is the fungal phytopathogen responsible for Septoria tritici leaf blotch (STB), the main foliar disease of wheat. Fungicides mitigate crop loss caused by STB, but multidrug-resistant Z. tritici strains pose a major threat to the global food supply …
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Rachel E. Hayward, Raymond F. Berkeley, Zijian Gao, Maximilian Garhammer et autres
Activity-based protein profiling has identified hundreds of proteins from diverse classes that react at specific cysteine residues with stereochemically defined electrophilic compounds (stereoprobes) in human cells. The structure-activity relationships underlying these stereoprobe-protein interactions, however, remain poorly understood. Here we show that the …
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Rebecca J. Chan, Xujun Cao, Sabrina L. Ergun, Evert Njomen et autres
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Daisuke Ogasawara, David Benjamin Konrad, Zher Yin Tan, Kimberly L. Carey et autres
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Sang Joon Won, Yuxiang Zhang, Christopher J. Reinhardt, Lauren M Hargis et autres
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Evert Njomen, Rachel E. Hayward, Kristen E. DeMeester, Daisuke Ogasawara et autres
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Lingyin Li, Rebecca J. Chan, Xujun Cao, Sabrina L. Ergun et autres
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Zhonglin Liu, Jarrett R. Remsberg, Haoxin Li, Evert Njomen et autres
Covalent chemistry coupled with activity-based protein profiling (ABPP) offers a versatile way to discover ligands for proteins in native biological systems. Here, we describe a set of stereo- and regiochemically defined spirocycle acrylamides and the analysis of these electrophilic "stereoprobes" in human …
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Sang Joon Won, Yuxiang Zhang, Christopher J. Reinhardt, Nicole S. MacRae et autres
Pioneer transcription factors (TFs) exhibit a specialized ability to bind to and open closed chromatin, facilitating engagement by other regulatory factors involved in gene activation or repression. Chemical probes are lacking for pioneer TFs, which has hindered their mechanistic investigation in cells. …
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Daisuke Ogasawara, David Benjamin Konrad, Zher Yin Tan, Kimberly L. Carey et autres
Chemical proteomics enables the global assessment of small molecule-protein interactions in native biological systems and has emerged as a versatile approach for ligand discovery. The range of small molecules explored by chemical proteomics has, however, been limited. Here, we describe a diversity-oriented …
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