ArticleMolecular cell2023
Proteomic discovery of chemical probes that perturb protein complexes in human cells.
Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 90 citations in OpenAlex.
- The cellular landscape of druggable RNA-binding proteins.Nature reviews. Drug discovery · 2026Review
- High-throughput ligand diversification to discover chemical inducers of proximity.Nature chemical biology · 2026Article
- REAL-TIME VISUALIZATION OF SPLICEOSOME ASSEMBLY REVEALS BASIC PRINCIPLES OF 3' SPLICE SITE SELECTION.Research square · 2026Article
- Systematic Targeting of Protein Complexes with Molecular COUPLrs.Cancer discovery · 2026Article
- A Global Ligandability Map of Tryptoline Butynamide Stereoprobes Identifies Covalent Inhibitors of the Actin Maturation Protease.Journal of the American Chemical Society · 2026Article
- High-resolution multi-omics enhances prediction and detection of smORF-encoded proteins in the human gut microbiome.Nature communications · 2026Article
- Complexoform-restricted covalent TRMT112 ligands that allosterically agonize METTL5.Nature chemical biology · 2026Article
- [Interferon-α induces disulfidptosis occurrence in human liver cancer cells].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Article
- Flipper: An advanced framework for identifying differential RNA binding behavior with eCLIP data.bioRxiv : the preprint server for biology · 2026Article
- A Global Ligandability Map of Tryptoline Butynamide Stereoprobes Identifies Covalent Inhibitors of the Actin Maturation Protease ACTMAP.bioRxiv : the preprint server for biology · 2026Article
- A Yeast-Based High-Throughput Screening Platform for the Discovery of Novel pre-mRNA Splicing Modulators.ACS chemical biology · 2026Article
- Cysteine Reactivity Profiling Identifies Host Regulators ofACS infectious diseases · 2026Article
- RNA Splicing as a Therapeutic Target in Cancer.Annual review of pharmacology and toxicology · 2026Review
- Stereoselective Degradation of Diacylglycerol Kinases Potentiate T cell Activation and Tumor Cell Cytotoxicity.bioRxiv : the preprint server for biology · 2025Article
- Proteome-Wide Discovery of Degradable Proteins Using Bifunctional Molecules.ACS central science · 2025Article
- Sulfinyl Aziridines as Stereoselective Covalent Destabilizing Degraders of the Oncogenic Transcription Factor MYC.Angewandte Chemie (International ed. in English) · 2025Article
- A Yeast-Based High-Throughput Screening Platform for the Discovery of Novel pre-mRNA Splicing Modulators.bioRxiv : the preprint server for biology · 2025Article
- Tryptoline Stereoprobe Elaboration Identifies Inhibitors of the GRPEL1-HSPA9 Chaperone Complex.bioRxiv : the preprint server for biology · 2025Article
- Target agnostic cellular screening in the era of chemically induced proximity.RSC medicinal chemistry · 2025Review
- Cysteine reactivity profiling identifies host regulators ofbioRxiv : the preprint server for biology · 2025Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
35 authors at 9 institutions in 2 countries.
Funding
Abstract
Most human proteins lack chemical probes, and several large-scale and generalizable small-molecule binding assays have been introduced to address this problem. How compounds discovered in such "binding-first" assays affect protein function, nonetheless, often remains unclear. Here, we describe a "function-first" proteomic strategy that uses size exclusion chromatography (SEC) to assess the global impact of electrophilic compounds on protein complexes in human cells. Integrating the SEC data with cysteine-directed activity-based protein profiling identifies changes in protein-protein interactions that are caused by site-specific liganding events, including the stereoselective engagement of cysteines in PSME1 and SF3B1 that disrupt the PA28 proteasome regulatory complex and stabilize a dynamic state of the spliceosome, respectively. Our findings thus show how multidimensional proteomic analysis of focused libraries of electrophilic compounds can expedite the discovery of chemical probes with site-specific functional effects on protein complexes in human cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.