ArticleACS infectious diseases2024
Studying Target-Engagement of Anti-Infectives by Solvent-Induced Protein Precipitation and Quantitative Mass Spectrometry.
Article in ACS infectious diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Solvent-induced partial cellular fixation decodes proteome-wide drug targets and downstream pathways in living cells.Nature communications · 2025Article
- Target identification of natural products in cancer with chemical proteomics and artificial intelligence approaches.Cancer biology & medicine · 2025Review
- Extracellular vesicles as vital players in drug delivery: a focus on clinical disease treatment.Frontiers in bioengineering and biotechnology · 2025Review
- Integral Solvent-Induced Protein Precipitation for Target-Engagement Studies inACS infectious diseases · 2024Article
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Authors and funding
13 authors.
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Abstract
Antimicrobial resistance (AMR) poses a serious threat to global health. The rapid emergence of resistance contrasts with the slow pace of antimicrobial development, emphasizing the urgent need for innovative drug discovery approaches. This study addresses a critical bottleneck in early drug development by introducing integral solvent-induced protein precipitation (iSPP) to rapidly assess the target-engagement of lead compounds in extracts of pathogenic microorganisms under close-to-physiological conditions. iSPP measures the change in protein stability against solvent-induced precipitation in the presence of ligands. The iSPP method for bacteria builds upon established SPP procedures and features optimized denaturation gradients and minimized sample input amounts. The effectiveness of the iSPP workflow was initially demonstrated through a multidrug target-engagement study. Using quantitative mass spectrometry (LC-MS/MS), we successfully identified known drug targets of seven different antibiotics in cell extracts of four AMR-related pathogens: the three Gram-negative bacteria
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