ArticleACS medicinal chemistry letters2017
Electrophilic Helical Peptides That Bond Covalently, Irreversibly, and Selectively in a Protein-Protein Interaction Site.
Article in ACS medicinal chemistry letters, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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
19 citing papers in PubMed, 32 citations in OpenAlex.
- Targeting "undruggable" cancer proteins: pharmacological challenges and emerging strategies.Translational cancer research · 2026Review
- An Intracellular Peptide Library Screening Platform Identifies Irreversible Covalent Transcription Factor Inhibitors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Identification of Covalent Cyclic Peptide Inhibitors Targeting Protein-Protein Interactions Using Phage Display.Journal of the American Chemical Society · 2025Article
- Identification of Covalent Cyclic Peptide Inhibitors Targeting Protein-Protein Interactions Using Phage Display.bioRxiv : the preprint server for biology · 2024Article
- Biospecific Chemistry for Covalent Linking of Biomacromolecules.Chemical reviews · 2024Review
- Advancing protein therapeutics through proximity-induced chemistry.Cell chemical biology · 2024Review
- Peptide-based covalent inhibitors of protein-protein interactions.Journal of peptide science : an official publication of the European Peptide Society · 2023Review
- Advanced approaches of developing targeted covalent drugs.RSC medicinal chemistry · 2022Review
- Rapid Covalent Labeling of Membrane Proteins on Living Cells Using a Nanobody-Epitope Tag Pair.Bioconjugate chemistry · 2022Article
- Targeting intracellular protein-protein interactions with macrocyclic peptides.Trends in pharmacological sciences · 2022Review
- Covalent and Noncovalent Targeting of the Tcf4/β-Catenin Strand Interface with β-Hairpin Mimics.ACS chemical biology · 2021Article
- Modular Approaches to Synthesize Activity- and Affinity-Based Chemical Probes.Frontiers in chemistry · 2021Review
- Covalent Targeting of Ras G12C by Rationally Designed Peptidomimetics.ACS chemical biology · 2020Article
- N-locking stabilization of covalent helical peptides: Application to Bfl-1 antagonists.Chemical biology & drug design · 2020Article
- A sulfonium tethered peptide ligand rapidly and selectively modifies protein cysteine in vicinity.Chemical science · 2019Article
- Precision Targeting of BFL-1/A1 and an ATM Co-dependency in Human Cancer.Cell reports · 2018Article
- Inhibitors of protein-protein interactions (PPIs): an analysis of scaffold choices and buried surface area.Current opinion in chemical biology · 2018Review
- Crystal Structures of Anti-apoptotic BFL-1 and Its Complex with a Covalent Stapled Peptide Inhibitor.Structure (London, England : 1993) · 2018Article
- Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein-protein interactions mediate most physiological and disease processes. Helix-constrained peptides potently mimic or inhibit these interactions by making multiple contacts over large surface areas. However, despite high affinities, they typically have short lifetimes bound to the protein. Here we insert both a helix-inducing constraint and an adjacent electrophile into the native peptide ligand BIM to target the oncogenic protein Bcl2A1. The modified BIM peptide bonds covalently and irreversibly to one cysteine within the helix-binding groove of Bcl2A1, but not to two other exposed cysteines on its surface, and shows no covalent bonding to other Bcl2 proteins. It also penetrates cell membranes and bonds covalently to Bcl2A1 inside cells. This innovative approach to increasing receptor residence time of helical peptides demonstrates the potential to selectively silence a PPI inside cells, with selectivity over other nucleophilic sites on 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.