ArticleJournal of the American Chemical Society2017
Diversity-Oriented Stapling Yields Intrinsically Cell-Penetrant Inducers of Autophagy.
Article in Journal of the American Chemical Society, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed.
- Membrane-Traversing Peptides: Mechanistic Landscapes, Assays, and Applications.Chemical reviews · 2026Review
- Fluorous oligoarginines as supra-enhancers for intracellular and transdermal peptide delivery.Bioactive materials · 2026Article
- Fluoroalkylated antimicrobial peptides enables cytosolic delivery and eradication of intracellular Staphylococcus aureus.Journal of nanobiotechnology · 2026Article
- Article
- Intrastrand Peptide Staples That Promote β-Sheet Folding, Self-Assembly, and Amyloid Seeding.Journal of the American Chemical Society · 2025Article
- Advances in Targeted Autophagy Modulation Strategies to Treat Cancer and Associated Treatment-Induced Cardiotoxicity.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Chemical tools to expand the ligandable proteome: Diversity-oriented synthesis-based photoreactive stereoprobes.Cell chemical biology · 2024Article
- Tackling Undruggable Targets with Designer Peptidomimetics and Synthetic Biologics.Chemical reviews · 2024Review
- Total Synthesis of Lipopeptide Bacilotetrin C: Discovery of Potent Anticancer Congeners Promoting Autophagy.ACS medicinal chemistry letters · 2024Article
- Synthesis of Membrane-Permeable Macrocyclic Peptides via Imidazopyridinium Grafting.Journal of the American Chemical Society · 2024Article
- Investigating the Cytosolic Delivery of Proteins by Lipid Nanoparticles Using the Chloroalkane Penetration Assay.Biochemistry · 2024Article
- Computational Prediction of Cyclic Peptide Structural Ensembles and Application to the Design of Keap1 Binders.Journal of chemical information and modeling · 2023Article
- Drug discovery by targeting the protein-protein interactions involved in autophagy.Acta pharmaceutica Sinica. B · 2023Review
- Identification of macrocyclic peptides which activate bacterial cylindrical proteases.RSC medicinal chemistry · 2023Article
- Liposomal Permeation Assay for Droplet-Scale Pharmacokinetic Screening.Journal of medicinal chemistry · 2023Article
- Adjusting Heterodimeric Coiled-Coils (K/E Zipper) to Connect Autophagy-Inducing Peptide with Cell-Penetrating Peptide.Pharmaceutics · 2023Article
- Amide-to-ester substitution as a stable alternative to N-methylation for increasing membrane permeability in cyclic peptides.Nature communications · 2023Article
- Rational design of Harakiri (HRK)-derived constrained peptides as BCL-xChemical communications (Cambridge, England) · 2023Article
- Aryl Fluorosulfate Based Inhibitors That Covalently Target the SIRT5 Lysine Deacylase.Angewandte Chemie (International ed. in English) · 2022Article
- Structure-Based Design of Stapled Peptides That Bind GABARAP and Inhibit Autophagy.Journal of the American Chemical Society · 2022Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Autophagy is an essential pathway by which cellular and foreign material are degraded and recycled in eukaryotic cells. Induction of autophagy is a promising approach for treating diverse human diseases, including neurodegenerative disorders and infectious diseases. Here, we report the use of a diversity-oriented stapling approach to produce autophagy-inducing peptides that are intrinsically cell-penetrant. These peptides induce autophagy at micromolar concentrations in vitro, have aggregate-clearing activity in a cellular model of Huntington's disease, and induce autophagy in vivo. Unexpectedly, the solution structure of the most potent stapled peptide, DD5-o, revealed an α-helical conformation in methanol, stabilized by an unusual (i,i+3) staple which cross-links two d-amino acids. We also developed a novel assay for cell penetration that reports exclusively on cytosolic access and used it to quantitatively compare the cell penetration of DD5-o and other autophagy-inducing peptides. These new, cell-penetrant autophagy inducers and their molecular details are critical advances in the effort to understand and control autophagy. More broadly, diversity-oriented stapling may provide a promising alternative to polycationic sequences as a means for rendering peptides more cell-penetrant.
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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.