ArticleProceedings of the National Academy of Sciences of the United States of America2004
A systematic method for identifying small-molecule modulators of protein-protein interactions.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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
42 citing papers in PubMed, 111 citations in OpenAlex.
- De Novo Discovery of Bioactive Cyclic Peptides via Cellular Selection of Genetically Encoded Libraries.Chembiochem : a European journal of chemical biology · 2026Review
- Bacterial two-hybrid systems evolved: innovations for protein-protein interaction research.Journal of bacteriology · 2025Review
- Rapid discovery of cyclic peptide protein aggregation inhibitors by continuous selection.Nature chemical biology · 2025Article
- Optimized Construction of a Yeast SICLOPPS Library for UnbiasedBiochemistry · 2024Article
- Tackling Undruggable Targets with Designer Peptidomimetics and Synthetic Biologics.Chemical reviews · 2024Review
- Identification and Development of Cyclic Peptide Inhibitors of Hypoxia Inducible Factors 1 and 2 That Disrupt Hypoxia-Response Signaling in Cancer Cells.Journal of the American Chemical Society · 2024Article
- An Autocatalytic Peptide Cyclase Improves Fidelity and Yield of Circular Peptides In Vivo and In Vitro.ACS synthetic biology · 2024Article
- High-Throughput Screening of Natural Product and Synthetic Molecule Libraries for Antibacterial Drug Discovery.Metabolites · 2023Review
- Characterisation of a cyclic peptide that binds to the RAS binding domain of phosphoinositide 3-kinase p110α.Scientific reports · 2023Article
- Head-to-tail cyclization of side chain-protected linear peptides to recapitulate genetically-encoded cyclized peptides.Peptide science (Hoboken, N.J.) · 2022Article
- Selection for constrained peptides that bind to a single target protein.Nature communications · 2021Article
- Expanding the Chemical Diversity of Genetically Encoded Libraries.ACS combinatorial science · 2020Article
- MOrPH-PhD: An Integrated Phage Display Platform for the Discovery of Functional Genetically Encoded Peptide Macrocycles.ACS central science · 2020Article
- Methods for generating and screening libraries of genetically encoded cyclic peptides in drug discovery.Nature reviews. Chemistry · 2020Review
- Evolving a Peptide: Library Platforms and Diversification Strategies.International journal of molecular sciences · 2019Review
- Review
- Inhibition of low-density lipoprotein receptor degradation with a cyclic peptide that disrupts the homodimerization of IDOL E3 ubiquitin ligase.Chemical science · 2018Article
- A promiscuous split intein with expanded protein engineering applications.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Targeting Bacillus anthracis toxicity with a genetically selected inhibitor of the PA/CMG2 protein-protein interaction.Scientific reports · 2017Article
- Macrocycles as protein-protein interaction inhibitors.The Biochemical journal · 2017Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Discovering small-molecule modulators of protein-protein interactions is a challenging task because of both the generally noncontiguous, large protein surfaces that form these interfaces and the shortage of high-throughput approaches capable of identifying such rare inhibitors. We describe here a robust and flexible methodology that couples disruption of protein-protein complexes to host cell survival. The feasibility of this approach was demonstrated through monitoring a small-molecule-mediated protein-protein association (FKBP12-rapamycin-FRAP) and two cases of dissociation (homodimeric HIV-1 protease and heterodimeric ribonucleotide reductase). For ribonucleotide reductase, we identified cyclic peptide inhibitors from genetically encoded libraries that dissociated the enzyme subunits. A solid-phase synthetic strategy and peptide ELISAs were developed to characterize these inhibitors, resulting in the discovery of cyclic peptides that operate in an unprecedented manner, thus highlighting the strengths of a functional approach. The ability of this method to process large libraries, coupled with the benefits of a genetic selection, allowed us to identify rare, uniquely active small-molecule modulators of protein-protein interactions at a frequency of less than one in 10 million.
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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.