ArticleNature communications2024
Design-rules for stapled peptides with in vivo activity and their application to Mdm2/X antagonists.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed.
- Peptides as programmable molecular scaffolds: from chemical synthesis and engineering to translational medicine.RSC chemical biology · 2026Review
- Targeting the Undruggable: Deep Learning-Driven Design of Peptide Therapeutics in Cancer.Pharmaceuticals (Basel, Switzerland) · 2026Review
- On-oligonucleotide olefin metathesis in water.Nature communications · 2026Article
- Integrative Peptide Drug Development: Chemical Engineering, AI-Driven Design, and Cell-Penetrating Peptides.Pharmaceutics · 2026Review
- Folded-state compatibility and unfolded-state constraint govern staple-based stabilization: guidelines from a coiled-coil model.RSC chemical biology · 2026Article
- Article
- Linker Engineering in Stapled Peptides for Enhanced Membrane Permeability: Screening and Optimization Strategies.International journal of molecular sciences · 2026Review
- Consequences of Peptide Macrocyclization Revealed by Virus-Inspired β-Hairpin Mimetics.ACS chemical biology · 2026Article
- Evaluating BindCraft for Generative Design of High-Affinity Peptides.ACS chemical biology · 2025Article
- A General Synthesis Approach to Double-Guanidinium Stapled Peptides and Foldamers.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Stapling of β-Glucans Increases Antibody Binding.Journal of the American Chemical Society · 2025Article
- Cyclic peptide structure prediction and design using AlphaFold2.Nature communications · 2025Article
- Optimal Stapling of a Helical Peptide-Foldamer Hybrid Using a C-Terminal 4-Mercaptoproline Enhances Protein Surface Recognition and Cellular Activity.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Interplay between CChembiochem : a European journal of chemical biology · 2025Article
- Unlocking the potential of tumor-targeting peptides in precision oncology.Oncology research · 2025Review
- 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
- Selection of Nucleotide-Encoded Mass Libraries of Macrocyclic Peptides for Inaccessible Drug Targets.Chemical reviews · 2024Review
- Structural Characterization of Disulfide-Linked p53-Derived Peptide Dimers.Research square · 2024Article
- MDM2/MDMX inhibition by Sulanemadlin synergizes with anti-Programmed Death 1 immunotherapy in wild-type p53 tumors.iScience · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
26 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although stapled α-helical peptides can address challenging targets, their advancement is impeded by poor understandings for making them cell permeable while avoiding off-target toxicities. By synthesizing >350 molecules, we present workflows for identifying stapled peptides against Mdm2(X) with in vivo activity and no off-target effects. Key insights include a clear correlation between lipophilicity and permeability, removal of positive charge to avoid off-target toxicities, judicious anionic residue placement to enhance solubility/behavior, optimization of C-terminal length/helicity to enhance potency, and optimization of staple type/number to avoid polypharmacology. Workflow application gives peptides with >292x improved cell proliferation potencies and no off-target cell proliferation effects ( > 3800x on-target index). Application of these 'design rules' to a distinct Mdm2(X) peptide series improves ( > 150x) cellular potencies and removes off-target toxicities. The outlined workflow should facilitate therapeutic impacts, especially for those targets such as Mdm2(X) that have hydrophobic interfaces and are targetable with a helical motif.
Indexed as
Identifiers
What OpenQuestion holds
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.