ArticleAngewandte Chemie (International ed. in English)2020
Fragment-Based Stabilizers of Protein-Protein Interactions through Imine-Based Tethering.
Article in Angewandte Chemie (International ed. in English), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 65 citations in OpenAlex.
- Restoring the 14-3-3/CRAF regulatory interaction in Noonan syndrome using molecular glues.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Modulation of the 14-3-3σ/C-RAF "Auto"inhibited Complex by Molecular Glues.Journal of the American Chemical Society · 2026Article
- The Current Toolbox for Covalent Inhibitors: From Hit Identification to Drug Discovery.JACS Au · 2025Review
- Stabilization of Native Protein-Protein Interactions with Molecular Glues: A 14-3-3 Case Study.Accounts of chemical research · 2025Article
- From Concepts to Inhibitors: A Blueprint for Targeting Protein-Protein Interactions.Chemical reviews · 2025Review
- Synthesis of Epoxyoxirenes: Phytotoxic Activity and Enzymatic Target Identification.Plants (Basel, Switzerland) · 2025Article
- Molecular glues of the regulatory ChREBP/14-3-3 complex protect beta cells from glucolipotoxicity.Nature communications · 2025Article
- Covalent Proximity Inducers.Chemical reviews · 2025Review
- Molecular glues of the regulatory ChREBP/14-3-3 complex protect beta cells from glucolipotoxicity.bioRxiv : the preprint server for biology · 2024Article
- Polymers for Disrupting Protein-Protein Interactions: Where Are We and Where Should We Be?Biomacromolecules · 2024Review
- Fragment-Based Interrogation of the 14-3-3/TAZ Protein-Protein Interaction.Biochemistry · 2024Article
- 14-3-3 Protein-Protein Interactions: From Mechanistic Understanding to Their Small-Molecule Stabilization.Chembiochem : a European journal of chemical biology · 2024Review
- Development of a NanoBRET assay for evaluation of 14-3-3σ molecular glues.SLAS discovery : advancing life sciences R & D · 2024Article
- Molecular glues for protein-protein interactions: Progressing toward a new dream.Cell chemical biology · 2024Review
- A simple method for developing lysine targeted covalent protein reagents.Nature communications · 2023Article
- Targeted Reversible Covalent Modification of a Noncatalytic Lysine of the Krev Interaction Trapped 1 Protein Enables Site-Directed Screening for Protein-Protein Interaction Inhibitors.ACS pharmacology & translational science · 2023Article
- C-terminal modification and functionalization of proteins via a self-cleavage tag triggered by a small molecule.Nature communications · 2023Article
- Structure-Based Optimization of Covalent, Small-Molecule Stabilizers of the 14-3-3σ/ERα Protein-Protein Interaction from Nonselective Fragments.Journal of the American Chemical Society · 2023Article
- From Tethered to Freestanding Stabilizers of 14-3-3 Protein-Protein Interactions through Fragment Linking.Angewandte Chemie (International ed. in English) · 2023Article
- Molecular Glue Discovery: Current and Future Approaches.Journal of medicinal chemistry · 2023Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small-molecule stabilization of protein-protein interactions (PPIs) is a promising concept in drug discovery, however the question how to identify or design chemical starting points in a "bottom-up" approach is largely unanswered. We report a novel concept for identifying initial chemical matter for PPI stabilization based on imine-forming fragments. The imine bond offers a covalent anchor for site-directed fragment targeting, whereas its transient nature enables efficient analysis of structure-activity relationships. This bond enables fragment identification and optimisation using protein crystallography. We report novel fragments that bind specifically to a lysine at the PPI interface of the p65-subunit-derived peptide of NF-κB with the adapter protein 14-3-3. Those fragments that subsequently establish contacts with the p65-derived peptide, rather than with 14-3-3, efficiently stabilize the 14-3-3/p65 complex and offer novel starting points for molecular glues.
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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.