ArticleNature communications2023
A simple method for developing lysine targeted covalent protein reagents.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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Who cites it
10 citing papers in PubMed, 28 citations in OpenAlex.
- Enhancing De Novo Designed Peptides and Proteins via Irreversible Covalent Isoquinolinium Capture.ACS chemical biology · 2026Article
- Dual-targeting pharmacological UFMylation inhibition reprograms tumor and immune microenvironments to achieve long-term glioblastoma regression.Signal transduction and targeted therapy · 2026Article
- EGFR inhibitor-resistant lung cancers exhibit collateral sensitivity to a covalent, cysteine-independent KEAP1 oligomerizing molecular bridge.Nature communications · 2026Article
- A Fragment-Based Electrophile-First Approach to Target Histidine with Aryl-Fluorosulfates: Application to hMcl-1.Journal of medicinal chemistry · 2025Article
- Computational Design of Lysine Targeting Covalent Binders Using Rosetta.Journal of chemical information and modeling · 2025Article
- Covalent Proximity Inducers.Chemical reviews · 2025Review
- Covalent Targeting of Histidine Residues with Aryl Fluorosulfates: Application to Mcl-1 BH3 Mimetics.Journal of medicinal chemistry · 2024Article
- Covalent Inhibition of a Host-Pathogen Protein-Protein Interaction Reduces the Infectivity ofJACS Au · 2024Article
- Genetically Encoded Epoxide Warhead for Precise and Versatile Covalent Targeting of Proteins.Journal of the American Chemical Society · 2024Article
- Tying the knot with lysine.Nature reviews. Chemistry · 2024Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Peptide-based covalent probes can target shallow protein surfaces not typically addressable using small molecules, yet there is a need for versatile approaches to convert native peptide sequences into covalent binders that can target a broad range of residues. Here we report protein-based thio-methacrylate esters-electrophiles that can be installed easily on unprotected peptides and proteins via cysteine side chains, and react efficiently and selectively with cysteine and lysine side chains on the target. Methacrylate phosphopeptides derived from 14-3-3-binding proteins irreversibly label 14-3-3σ via either lysine or cysteine residues, depending on the position of the electrophile. Methacrylate peptides targeting a conserved lysine residue exhibit pan-isoform binding of 14-3-3 proteins both in lysates and in extracellular media. Finally, we apply this approach to develop protein-based covalent binders. A methacrylate-modified variant of the colicin E9 immunity protein irreversibly binds to the E9 DNAse, resulting in significantly higher thermal stability relative to the non-covalent complex. Our approach offers a simple and versatile route to convert peptides and proteins into potent covalent binders.
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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.