ArticleNature chemical biology2023
Nucleophilic covalent ligand discovery for the cysteine redoxome.
Article in Nature chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 36 citations in OpenAlex.
- Substrate-Derived Peptides for Selective Covalent Inhibition of Protein Tyrosine Kinases.ACS chemical biology · 2026Article
- Article
- A druggable redox switch on SHP1 controls macrophage inflammation.Nature chemical biology · 2026Article
- Substrate-derived peptides for selective covalent inhibition of protein tyrosine kinases.bioRxiv : the preprint server for biology · 2026Article
- Proteome-wide mapping of cysteine persulfidation in deep-sea hyperthermophilic archaea.Extremophiles : life under extreme conditions · 2026Article
- Friends, foes and signals.Nature chemical biology · 2026Article
- Defining and refining the cysteine redoxome through sulfur chemical biology.Nature chemical biology · 2026Review
- A druggable redox switch on SHP1 controls macrophage inflammation.bioRxiv : the preprint server for biology · 2026Article
- Chemical Proteomics Reveals Regulation of Bile Salt Hydrolases via Oxidative Post-translational Modifications.Journal of the American Chemical Society · 2026Article
- Global profiling of arginine reactivity and ligandability in the human proteome.Nature chemistry · 2026Article
- Proteomic Profiling of Oxidative Stress Response Proteins with a Methionine Sulfoxide-Inspired Activity-Based Probe.JACS Au · 2026Article
- Chemical proteomics reveals regulation of bile salt hydrolases via oxidative post-translational modifications.bioRxiv : the preprint server for biology · 2025Article
- Cysteine-enabled cleavability to advance cross-linking mass spectrometry for global analysis of endogenous protein-protein interactions.Nature communications · 2025Article
- Targeting the Reactive Proteome: Recent Advances in Activity-Based Protein Profiling and Probe Design.Biomolecules · 2025Review
- One-step labeling with a fluorinated porphyrin-based probe enablesInnovation (Cambridge (Mass.)) · 2025Article
- Bioorthogonal Probe BTD-Az Enables Sensitive and Rapid In Vivo Profiling of Protein Cysteine Sulfenylation.Bioconjugate chemistry · 2025Article
- Pan-microalgal dark proteome mapping via interpretable deep learning and synthetic chimeras.Patterns (New York, N.Y.) · 2025Article
- Profiling the landscape of cysteine posttranslational modifications in brain aging and neurodegeneration.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- CySP3-96 Enables Scalable, Streamlined, and Low-Cost Sample Preparation for Cysteine Chemoproteomic Applications.Molecular & cellular proteomics : MCP · 2025Article
- Redox Regulation of cAMP-Dependent Protein Kinase and Its Role in Health and Disease.Life (Basel, Switzerland) · 2025Review
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
With an eye toward expanding chemistries used for covalent ligand discovery, we elaborated an umpolung strategy that exploits the 'polarity reversal' of sulfur when cysteine is oxidized to sulfenic acid, a widespread post-translational modification, for selective bioconjugation with C-nucleophiles. Here we present a global map of a human sulfenome that is susceptible to covalent modification by members of a nucleophilic fragment library. More than 500 liganded sulfenic acids were identified on proteins across diverse functional classes, and, of these, more than 80% were not targeted by electrophilic fragment analogs. We further show that members of our nucleophilic fragment library can impair functional protein-protein interactions involved in nuclear oncoprotein transport and DNA damage repair. Our findings reveal a vast expanse of ligandable sulfenic acids in the human proteome and highlight the utility of nucleophilic small molecules in the fragment-based covalent ligand discovery pipeline, presaging further opportunities using non-traditional chemistries for targeting proteins.
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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.