ArticleACS central science2021
Functionalized Scout Fragments for Site-Specific Covalent Ligand Discovery and Optimization.
Article in ACS central science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 55 citations in OpenAlex.
- Proteome-Wide Target Identification Using Reactive Metallo-Scaffolds (r-mS): A Platform for Metallodrug Discovery.Angewandte Chemie (International ed. in English) · 2026Article
- Next-generation multiplexed targeted proteomics quantifies post-translational modifications in disease and compound-protein interactions with high throughput.Nature communications · 2026Article
- Expanding the repertoire of chemically induced covalent neoantigens.Nature chemical biology · 2026Article
- Modular Rh-Catalyzed Synthesis and Biological Profiling of Diverse Pentafluorobenzenesulfonamide Reactive Fragments.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- α-Halothioamide warheads with enhanced cysteine reactivity and specificity for covalent protein labelling.Nature communications · 2026Article
- WRN structural flexibility showcased through fragment-based lead discovery of inhibitors.Nature communications · 2026Article
- Discovery of RNA-Reactive Small Molecules Guides the Design of Electrophilic Modules for RNA-Specific Covalent Binders.Journal of the American Chemical Society · 2025Article
- Next-Generation Multiplexed Targeted Proteomics Quantifies Post-Translational Modifications, Compound-Protein Interactions, and Disease Biomarkers with High Throughput.bioRxiv : the preprint server for biology · 2025Article
- Discovery of DCAF16 Binders for Targeted Protein Degradation.ACS chemical biology · 2025Article
- Covalent targeting of splicing in T cells.Cell chemical biology · 2025Article
- Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads.Beilstein journal of organic chemistry · 2025Article
- Chemical proteomic mapping of reversible small molecule binding sites in native systems.Trends in pharmacological sciences · 2024Review
- Discovery of Trypanosoma brucei inhibitors enabled by a unified synthesis of diverse sulfonyl fluorides.Communications chemistry · 2024Article
- Charting the ligandable proteome for stereoselective interactions.Nature chemistry · 2024Article
- Ligand discovery by activity-based protein profiling.Cell chemical biology · 2024Review
- Targeted protein degradation: from mechanisms to clinic.Nature reviews. Molecular cell biology · 2024Review
- Contribution of Noncovalent Recognition and Reactivity to the Optimization of Covalent Inhibitors: A Case Study on KRasACS chemical biology · 2024Article
- Targeted Protein Degradation: Current and Emerging Approaches for E3 Ligase Deconvolution.Journal of medicinal chemistry · 2024Review
- Enhanced mapping of small-molecule binding sites in cells.Nature chemical biology · 2024Article
- Chemical Proteomics-Guided Discovery of Covalent Ligands for Cancer Proteins.Annual review of cancer biology · 2024Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Covalent ligands are a versatile class of chemical probes and drugs that can target noncanonical sites on proteins and display differentiated pharmacodynamic properties. Chemical proteomic methods have been introduced that leverage electrophilic fragments to globally profile the covalent ligandability of nucleophilic residues, such as cysteine and lysine, in native biological systems. Further optimization of these initial ligandability events without resorting to the time-consuming process of individualized protein purification and functional assay development, however, presents a persistent technical challenge. Here, we show that broadly reactive electrophilic fragments, or "scouts", can be converted into site-specific target engagement probes for screening small molecules against a wide array of proteins in convenient gel- and ELISA-based assay formats. We use these assays to expediently optimize a weak potency fragment hit into a sub-μM inhibitor that selectively engages an active-site cysteine in the retinaldehyde reductase AKR1B10. Our findings provide a road map to optimize covalent fragments into more advanced chemical probes without requiring protein purification or structural analysis.
Identifiers
What OpenQuestion holds
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.