ArticleNature chemical biology2016
Biophysical determinants for cellular uptake of hydrocarbon-stapled peptide helices.
Article in Nature chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 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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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
105 citing papers in PubMed.
- Targeting LKB1-inactivated lung cancers with a stapled peptide inhibitor of the CRTC-CREB pathway.Molecular therapy. Oncology · 2026Article
- Protein Modifications for Cellular Protein Delivery.Chemical reviews · 2026Review
- Linker Engineering in Stapled Peptides for Enhanced Membrane Permeability: Screening and Optimization Strategies.International journal of molecular sciences · 2026Review
- Article
- Polymicrobial Biofilms: Interkingdom Interactions, Resistance and Therapeutic Strategies.Microbial biotechnology · 2025Review
- Deep-Learning-Based Approaches for Rational Design of Stapled Peptides With High Antimicrobial Activity and Stability.Microbial biotechnology · 2025Article
- Direct inhibition of tumor hypoxia response with synthetic transcriptional repressors.Nature chemical biology · 2025Article
- Exploring the Chemical Features and Biomedical Relevance of Cell-Penetrating Peptides.International journal of molecular sciences · 2024Review
- Tackling Undruggable Targets with Designer Peptidomimetics and Synthetic Biologics.Chemical reviews · 2024Review
- The Role of Structural Flexibility in Hydrocarbon-Stapled Peptides Designed to Block Viral Infection via Human ACE2 Mimicry.Peptide science (Hoboken, N.J.) · 2024Article
- Dissecting the neuroprotective interaction between the BH4 domain of BCL-w and the IP3 receptor.Cell chemical biology · 2024Article
- Targeted Degradation of Protein Kinase A via a Stapled Peptide PROTAC.ACS chemical biology · 2024Article
- Recent advances in methods for quantifying the cell penetration of macromolecules.Current opinion in chemical biology · 2024Review
- Comparing Cell Penetration of Biotherapeutics across Human Cell Lines.ACS chemical biology · 2024Article
- Histidine-Covalent Stapled Alpha-Helical Peptides Targeting hMcl-1.Journal of medicinal chemistry · 2024Article
- Development of an α-Klotho Recognizing High-Affinity Peptide Probe from In-Solution Enrichment.JACS Au · 2024Article
- Machine learning to predict continuous protein properties from binary cell sorting data and map unseen sequence space.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Cytosolic Delivery of Bioactive Cyclic Peptide Cargo by Spontaneous Membrane Translocating Peptides.ACS omega · 2024Article
- Helical peptides with disordered regions for measles viruses provide new generalized insights into fusion inhibitors.iScience · 2024Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Hydrocarbon-stapled peptides are a class of bioactive alpha-helical ligands developed to dissect and target protein interactions. While there is consensus that stapled peptides can be effective chemical tools for investigating protein regulation, their broader utility for therapeutic modulation of intracellular interactions remains an active area of study. In particular, the design principles for generating cell-permeable stapled peptides are empiric, yet consistent intracellular access is essential to in vivo application. Here, we used an unbiased statistical approach to determine which biophysical parameters dictate the uptake of stapled-peptide libraries. We found that staple placement at the amphipathic boundary combined with optimal hydrophobic and helical content are the key drivers of cellular uptake, whereas excess hydrophobicity and positive charge at isolated amino acid positions can trigger membrane lysis at elevated peptide dosing. Our results provide a design roadmap for maximizing the potential to generate cell-permeable stapled peptides with on-mechanism cellular activity.
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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.