ReviewChemical science2021
Peptide-based inhibitors of protein-protein interactions: biophysical, structural and cellular consequences of introducing a constraint.
Review in Chemical science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 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.
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.
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Who cites it
53 citing papers in PubMed, 119 citations in OpenAlex.
- De Novo Discovery of Nonstandard Thioisoindole-Bridged Bicyclic Peptides Targeting Traf2- and NCK-Interacting Kinase.Angewandte Chemie (International ed. in English) · 2026Article
- NADPH oxidases in immunometabolism and disease pathology: mechanistic networks, pollutant triggers, and therapeutic frontiers.Cellular & molecular immunology · 2026Review
- Multi-Site Aggregation of p53: Insights from Self- and Co-Aggregation of Multiple Aggregation-Prone Regions.ACS omega · 2026Article
- Computationally Evidence-Grounded Sequence-First Design of Peptide Binders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Dose-Dependent Influence of RBD-Derived Amyloidogenic Peptides on SARS-CoV-2 Infectivity: A Cautionary Tale for Antiviral Design.International journal of molecular sciences · 2026Article
- PpF: a density functional fine-tuned for noncovalent interactions of protein and peptide residues.Chemical science · 2026Article
- MinimalRSC chemical biology · 2026Article
- Cyclic Peptides as Modulators of Protein-Protein Interactions: A Survival Guide from Discovery Platforms to AI-Driven Design.International journal of molecular sciences · 2026Review
- The critical role of the RUNX1/NF-κB transcriptional complex-mediated PVAT-VSMC axis in aortic dissection.Journal of cardiothoracic surgery · 2026Review
- Discovery of SHANK1-PDZ Peptide-Fragment Inhibitors Using a Dynamic Ligation Screening Strategy.Biochemistry · 2026Article
- Design and biological evaluation of peptide disruptors targeting YAP1-TEAD interaction for oral cancer.BMC oral health · 2025Article
- A novel D-peptide modulates DCLK1 gelsolin interactions, reducing PDAC tumor growth.Scientific reports · 2025Article
- An Orally Available Grafted Peptide Targeting Epidermal Growth Factor Receptor Dimers Reduces Non-Small Cell Lung Cancer Tumors in Mouse Models.ACS pharmacology & translational science · 2025Article
- Breaking the oncogenic alliance: advances in disrupting the MTDH-SND1 complex for cancer therapy.RSC advances · 2025Review
- Innovative Peptide Therapeutics in the Pipeline: Transforming Cancer Detection and Treatment.International journal of molecular sciences · 2025Review
- Grafted Coiled-Coil Peptides as Multivalent Scaffolds for Protein Recognition.ACS chemical biology · 2025Article
- The Potential of Peptide-Based Inhibitors in Disrupting Protein-Protein Interactions for Targeted Cancer Therapy.International journal of molecular sciences · 2025Review
- Advancements in Loop Cyclization Approaches for Enhanced Peptide Therapeutics for Targeting Protein-Protein Interactions.The Journal of organic chemistry · 2025Article
- Novel peptide inhibitor for the Chikungunya virus nsP2 protease: Identification and characterization.Current research in microbial sciences · 2025Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein-protein interactions (PPIs) are implicated in the majority of cellular processes by enabling and regulating the function of individual proteins. Thus, PPIs represent high-value, but challenging targets for therapeutic intervention. The development of constrained peptides represents an emerging strategy to generate peptide-based PPI inhibitors, typically mediated by α-helices. The approach can confer significant benefits including enhanced affinity, stability and cellular penetration and is ingrained in the premise that pre-organization simultaneously pays the entropic cost of binding, prevents a peptide from adopting a protease compliant β-strand conformation and shields the hydrophilic amides from the hydrophobic membrane. This conceptual blueprint for the empirical design of peptide-based PPI inhibitors is an exciting and potentially lucrative way to effect successful PPI inhibitor drug-discovery. However, a plethora of more subtle effects may arise from the introduction of a constraint that include changes to binding dynamics, the mode of recognition and molecular properties. In this review, we summarise the influence of inserting constraints on biophysical, conformational, structural and cellular behaviour across a range of constraining chemistries and targets, to highlight the tremendous success that has been achieved with constrained peptides alongside emerging design opportunities and challenges.
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.