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| http://dx.doi.org/10.3389/fpls.2024.1506569 | DOI Listing |
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Robust proteome profiling of cysteine-reactive fragments using label-free chemoproteomics.
Nat Commun
January 2025
Crick-GSK Biomedical LinkLabs, GSK, Gunnels Wood Road, Stevenage, Hertfordshire, UK.
Identifying pharmacological probes for human proteins represents a key opportunity to accelerate the discovery of new therapeutics. High-content screening approaches to expand the ligandable proteome offer the potential to expedite the discovery of novel chemical probes to study protein function. Screening libraries of reactive fragments by chemoproteomics offers a compelling approach to ligand discovery, however, optimising sample throughput, proteomic depth, and data reproducibility remains a key challenge.
View Article and Find Full Text PDFPhenomics-based Discovery of Novel Orthosteric Choline Kinase Inhibitors.
Angew Chem Int Ed Engl
December 2024
University of Oxford, Nuffield Department of Medicine, Centre for Medicines Discovery, NDM Research Building, Roosevelt Drive, OX3 7FZ, Oxford, UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND.
Article Synopsis
- CHKA is a key player in cell metabolism and is linked to cancer and immune function, but developing effective inhibitors has been challenging.
- Researchers discovered that CHKA is an off-target for specific inhibitors, which helps clarify previous inconsistencies in related studies.
- Modulating CHKA affects immune responses, particularly B-cell maturation and IgG secretion, indicating its significant role in immune signaling.
Quantitative profiling of PTM stoichiometry by DNA mass tags.
Bioorg Med Chem
December 2024
Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China. Electronic address:
Article Synopsis
- Protein post-translational modification (PTM) is crucial for regulating protein function, and understanding the proportion of modified proteins, known as PTM stoichiometry, is important for studying these modifications.
- The researchers developed a new method called "STO-MS+" that improves upon the original "STO-MS" technique by using a better mass tag and a label-free analysis to enhance measurement efficiency and precision.
- STO-MS+ was successfully applied to measure the stoichiometry of three specific PTMs, showcasing significant advancements in the analysis of post-translational modifications in biological samples.
CySP3-96 enables scalable, streamlined, and low-cost sample preparation for cysteine chemoproteomic applications.
Mol Cell Proteomics
December 2024
Biological Chemistry Department, David Geffen School of Medicine, UCLA, Los Angeles, CA, 90095, USA; Department of Chemistry and Biochemistry, UCLA, Los Angeles, CA, 90095, USA; Molecular Biology Institute, UCLA, Los Angeles, CA, 90095, USA; DOE Institute for Genomics and Proteomics, UCLA, Los Angeles, CA, 90095, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA, 90095, USA. Electronic address:
Cysteine chemoproteomic screening platforms are widely utilized for chemical probe and drug discovery campaigns. Chemoproteomic compound screens, which use a mass spectrometry-based proteomic readout, can interrogate the structure activity relationship (SAR) for thousands of proteins in parallel across the proteome. The versatility of chemoproteomic screens has been demonstrated across electrophilic, nucleophilic, and reversible classes of molecules.
View Article and Find Full Text PDFChemoproteomics approach to elucidating biosynthetic pathway of plant natural products.
Front Plant Sci
November 2024
National Tobacco Cultivation, Physiology and Biochemistry Research Center, Flavors and Fragrance Engineering and Technology Research Center of Henan Province, College of Tobacco Science, Henan Agricultural University, Zhengzhou, Henan, China.
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