ArticleNature chemistry2021
A proteome-wide atlas of lysine-reactive chemistry.
Article in Nature chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 113 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.
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Who cites it
113 citing papers in PubMed, 242 citations in OpenAlex.
- Progress and challenges in traceless ligand-directed labelling chemistry.Communications chemistry · 2026Review
- Secondary-Amine Relay Enables Lysine-Directed Multicomponent Functionalization of Peptides.JACS Au · 2026Article
- Article
- Precision Chemistry for Protein Lysine Modification.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Review
- Cyclopropanol can function as a caged dual-functional warhead for selective electrochemical bioconjugation.Nature chemistry · 2026Article
- Expanding the repertoire of chemically induced covalent neoantigens.Nature chemical biology · 2026Article
- Analysis of Confounding Factors in Reactive Cysteine Profiling Reveals Enhanced Chromatin-Protein Association via CDK7 Inhibition by THZ1.ACS chemical biology · 2026Article
- Scaling covalent ligand discovery through dynamic combinatorial library-versus-proteome screening.Nature communications · 2026Article
- Mapping Functionally Relevant Tractable Lysines of Challenging Protein Targets by Covalent Fragment Screening.Chembiochem : a European journal of chemical biology · 2026Article
- Article
- A Global Ligandability Map of Tryptoline Butynamide Stereoprobes Identifies Covalent Inhibitors of the Actin Maturation Protease.Journal of the American Chemical Society · 2026Article
- Targeting a Pleckstrin Homology Domain with a Lysine-Reactive Covalent Binder.Journal of medicinal chemistry · 2026Article
- α-Halothioamide warheads with enhanced cysteine reactivity and specificity for covalent protein labelling.Nature communications · 2026Article
- Tunable Cell Surface Proximity Labeling via Photocatalytic and Enzymatic Activation of Fast Bioorthogonal Chemistry.Journal of the American Chemical Society · 2026Article
- Proteome-wide mapping of cysteine persulfidation in deep-sea hyperthermophilic archaea.Extremophiles : life under extreme conditions · 2026Article
- Cooperative Aldehyde Chemistry Maps an Orthogonal Lysine Reactivity Landscape.Journal of the American Chemical Society · 2026Article
- Attempts to Achieve Targeted Covalent Inhibition of Hsp90β.Chemical biology & drug design · 2026Article
- Mapping the SHP2 Allosteric Pocket With Target-Biased Covalent Fragments.Chembiochem : a European journal of chemical biology · 2026Article
- Quantitative Mapping of NHS Ester-Protein Reactivity Using Native Top-Down Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 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
53 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Recent advances in chemical proteomics have begun to characterize the reactivity and ligandability of lysines on a global scale. Yet, only a limited diversity of aminophilic electrophiles have been evaluated for interactions with the lysine proteome. Here, we report an in-depth profiling of >30 uncharted aminophilic chemotypes that greatly expands the content of ligandable lysines in human proteins. Aminophilic electrophiles showed disparate proteomic reactivities that range from selective interactions with a handful of lysines to, for a set of dicarboxaldehyde fragments, remarkably broad engagement of the covalent small-molecule-lysine interactions captured by the entire library. We used these latter 'scout' electrophiles to efficiently map ligandable lysines in primary human immune cells under stimulatory conditions. Finally, we show that aminophilic compounds perturb diverse biochemical functions through site-selective modification of lysines in proteins, including protein-RNA interactions implicated in innate immune responses. These findings support the broad potential of covalent chemistry for targeting functional lysines in the human proteome.
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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.