ArticleScientific reports2017
Enhancing Specific Disruption of Intracellular Protein Complexes by Hydrocarbon Stapled Peptides Using Lipid Based Delivery.
Article in Scientific reports, 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, 30 citations in OpenAlex.
- Extracellular Vesicle-Mediated Delivery of Constrained Peptides Disrupts the Pathogenic Interaction of LRRK2-FADD in Parkinson's Disease.Journal of extracellular biology · 2026Article
- Targeted Degradation of Protein Kinase A via a Stapled Peptide PROTAC.ACS chemical biology · 2024Article
- Chimeric Protein Switch Biosensors.Advances in biochemical engineering/biotechnology · 2024Review
- Stapled peptides as scaffolds for developing radiotracers for intracellular targets: Preliminary evaluation of a radioiodinated MDM2-binding stapled peptide in the SJSA-1 osteosarcoma model.Bioorganic & medicinal chemistry letters · 2022Article
- Fluorine-18 Labeling of the MDM2 Inhibitor RG7388 for PET Imaging: Chemistry and Preliminary Evaluation.Molecular pharmaceutics · 2021Article
- Possible Therapeutic Strategy Involving the Purine Synthesis Pathway Regulated by ITK in Tongue Squamous Cell Carcinoma.Cancers · 2021Article
- Feasibility of Developing Radiotracers for MDM2: Synthesis and Preliminary Evaluation of anPharmaceuticals (Basel, Switzerland) · 2021Article
- De-risking Drug Discovery of Intracellular Targeting Peptides: Screening Strategies to Eliminate False-Positive Hits.ACS medicinal chemistry letters · 2020Article
- Construction of a Stapled α-Helix Peptide Library Displayed on Phage for the Screening of Galectin-3-Binding Peptide Ligands.ACS omega · 2020Article
- Simultaneous measurement of p53:Mdm2 and p53:Mdm4 protein-protein interactions in whole cells using fluorescence labelled foci.Scientific reports · 2019Article
- Understanding Cell Penetration of Cyclic Peptides.Chemical reviews · 2019Review
- A new strategy for the in vitro selection of stapled peptide inhibitors by mRNA display.Chemical communications (Cambridge, England) · 2019Article
- Stereoisomerism of stapled peptide inhibitors of the p53-Mdm2 interaction: an assessment of synthetic strategies and activity profiles.Chemical science · 2019Article
- Monitoring flux in signalling pathways through measurements of 4EBP1-mediated eIF4F complex assembly.BMC biology · 2019Article
- Hitting Undruggable Targets: Viewing Stabilized Peptide Development through the Lens of Quantitative Systems Pharmacology.Trends in biochemical sciences · 2019Review
- Stapled Peptides Inhibitors: A New Window for Target Drug Discovery.Computational and structural biotechnology journal · 2019Review
- Constrained α-Helical Peptides as Inhibitors of Protein-Protein and Protein-DNA Interactions.Biomedicines · 2018Review
- Synthetic 10FN3-based mono- and bivalent inhibitors of MDM2/X function.Protein engineering, design & selection : PEDS · 2018Article
- FaptaSyme: A Strategy for Converting a Monomer/Oligomer-Nonselective Aptameric Sensor into an Oligomer-Selective One.Chembiochem : a European journal of chemical biology · 2018Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Linear peptides can mimic and disrupt protein-protein interactions involved in critical cell signaling pathways. Such peptides however are usually protease sensitive and unable to engage with intracellular targets due to lack of membrane permeability. Peptide stapling has been proposed to circumvent these limitations but recent data has suggested that this method does not universally solve the problem of cell entry and can lead to molecules with off target cell lytic properties. To address these issues a library of stapled peptides was synthesized and screened to identify compounds that bound Mdm2 and activated cellular p53. A lead peptide was identified that activated intracellular p53 with negligible nonspecific cytotoxicity, however it still bound serum avidly and only showed a marginal improvement in cellular potency. These hurdles were overcome by successfully identifying a pyridinium-based cationic lipid formulation, which significantly improved the activity of the stapled peptide in a p53 reporter cell line, principally through increased vesicular escape. These studies underscore that stapled peptides, which are cell permeable and target specific, can be identified with rigorous experimental design and that these properties can be improved through use with lipid based formulations. This work should facilitate the clinical translation of stapled peptides.
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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.