ArticleNature chemistry2019
De novo macrocyclic peptides that specifically modulate Lys48-linked ubiquitin chains.
Article in Nature chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- Cell-Free Approach for Non-canonical Amino Acids Incorporation Into Polypeptides.Frontiers in bioengineering and biotechnology · 2020Pooled it
- StrEAMM-Thioether: Efficient Structure Prediction for Thioether-Linked Cyclic Peptides.The journal of physical chemistry. B · 2026Article
- The Molecular Toolbox for Linkage Type-Specific Analysis of Ubiquitin Signaling.Chembiochem : a European journal of chemical biology · 2025Review
- Mirror-Image Random Nonstandard Peptides Integrated Discovery (MI-RaPID) Technology Yields Highly Stable and Selective Macrocyclic Peptide Inhibitors for Matrix Metallopeptidase 7.Angewandte Chemie (International ed. in English) · 2025Article
- Light-Activatable Ubiquitin for Studying Linkage-Specific Ubiquitin Chain Formation Kinetics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Tackling Undruggable Targets with Designer Peptidomimetics and Synthetic Biologics.Chemical reviews · 2024Review
- OTUB1 regulation of ferroptosis and the protective role of ferrostatin-1 in lupus nephritis.Cell death & disease · 2024Article
- Encoding and display technologies for combinatorial libraries in drug discovery: The coming of age from biology to therapy.Acta pharmaceutica Sinica. B · 2024Review
- Diverse roles of UBE2S in cancer and therapy resistance: Biological functions and mechanisms.Heliyon · 2024Review
- DCAF13 inhibits the p53 signaling pathway by promoting p53 ubiquitination modification in lung adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2024Article
- Mechanism of selective recognition of Lys48-linked polyubiquitin by macrocyclic peptide inhibitors of proteasomal degradation.Nature communications · 2023Article
- Combining Chemical Protein Synthesis and Random Nonstandard Peptides Integrated Discovery for Modulating Biological Processes.Accounts of chemical research · 2023Article
- A macrocyclic peptide inhibitor traps MRP1 in a catalytically incompetent conformation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Selective macrocyclic peptide modulators of Lys63-linked ubiquitin chains disrupt DNA damage repair.Nature communications · 2022Article
- A context-dependent and disordered ubiquitin-binding motif.Cellular and molecular life sciences : CMLS · 2022Article
- Potent macrocycle inhibitors of the human SAGA deubiquitinating module.Cell chemical biology · 2022Article
- 2-Pyridine Carboxaldehyde for Semi-Automated Soft Spot Identification in Cyclic Peptides.International journal of molecular sciences · 2022Article
- Targeting intracellular protein-protein interactions with macrocyclic peptides.Trends in pharmacological sciences · 2022Review
- MOrPH-PhD: A Phage Display System for the Functional Selection of Genetically Encoded Macrocyclic Peptides.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Cell-Free PURE System: Evolution and Achievements.Biodesign research · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
A promising approach in cancer therapy is to find ligands that directly bind ubiquitin (Ub) chains. However, finding molecules capable of tightly and specifically binding Ub chains is challenging given the range of Ub polymer lengths and linkages and their subtle structural differences. Here, we use total chemical synthesis of proteins to generate highly homogeneous Ub chains for screening against trillion-member macrocyclic peptide libraries (RaPID system). De novo cyclic peptides were found that can bind tightly and specifically to K48-linked Ub chains, confirmed by NMR studies. These cyclic peptides protected K48-linked Ub chains from deubiquitinating enzymes and prevented proteasomal degradation of Ub-tagged proteins. The cyclic peptides could enter cells, inhibit growth and induce programmed cell death, opening new opportunities for therapeutic intervention. This highly synthetic approach, with both protein target generation and cyclic peptide discovery performed in vitro, will make other elaborate post-translationally modified targets accessible for drug discovery.
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.