ArticleChemical science2019
Ureidopeptide GLP-1 analogues with prolonged activity
Article in Chemical science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 38 citations in OpenAlex.
- Potent and biased agonists of class B1 GPCRs from a heterochiral design strategy.Nature chemistry · 2026Article
- Discovery of Biased Dual-Agonists of Glucagon-Like Peptide 1 and Glucagon Receptors through Mutation of a Conserved Aspartate.ACS medicinal chemistry letters · 2026Article
- Structural basis of PTH1R-β-arrestin core engagement reveals design principles for G-protein-biased therapeutics.Nature structural & molecular biology · 2026Article
- Modelling G protein-biased agonism using GLP-1 receptor C-terminal mutations.Molecular metabolism · 2026Article
- Prolonged signaling of backbone-modified glucagon-like peptide-Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Comparison of Exendin-4 and Its Single Amino Acid Substitutions as Parent Peptides for GLP-1 Receptor Imaging Probes.Molecules (Basel, Switzerland) · 2025Article
- Stereochemical insights into β-amino-RSC advances · 2024Article
- Hormone Analogues with Unique Signaling Profiles from Replacement of α-Residue Triads with β/γ Diads.Journal of the American Chemical Society · 2023Article
- Unnatural helical peptidic foldamers as protein segment mimics.Chemical Society reviews · 2023Review
- New Insights into the Structure and Function of Class B1 GPCRs.Endocrine reviews · 2023Article
- Article
- In vivo and in vitro characterization of GL0034, a novel long-acting glucagon-like peptide-1 receptor agonist.Diabetes, obesity & metabolism · 2022Article
- Structural and functional diversity among agonist-bound states of the GLP-1 receptor.Nature chemical biology · 2022Article
- The therapeutic potential of GLP-1 receptor biased agonism.British journal of pharmacology · 2022 · on this mapReview
- Acylation of the Incretin Peptide Exendin-4 Directly Impacts Glucagon-Like Peptide-1 Receptor Signaling and Trafficking.Molecular pharmacology · 2021Article
- Partial agonism improves the anti-hyperglycaemic efficacy of an oxyntomodulin-derived GLP-1R/GCGR co-agonist.Molecular metabolism · 2021Article
- Evaluation of efficacy- versus affinity-driven agonism with biased GLP-1R ligands P5 and exendin-F1.Biochemical pharmacology · 2021Article
- The Interplay of Glucagon-Like Peptide-1 Receptor Trafficking and Signalling in Pancreatic Beta Cells.Frontiers in endocrinology · 2021Review
- Ligand-Specific Factors Influencing GLP-1 Receptor Post-Endocytic Trafficking and Degradation in Pancreatic Beta Cells.International journal of molecular sciences · 2020Article
- Signalling, trafficking and glucoregulatory properties of glucagon-like peptide-1 receptor agonists exendin-4 and lixisenatide.British journal of pharmacology · 2020Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
The high demand of the pharmaceutical industry for new modalities to address the diversification of biological targets with large surfaces of interaction led us to investigate the replacement of α-amino acid residues with ureido units at selected positions in peptides to improve potency and generate effective incretin mimics. Based on molecular dynamics simulations, N-terminally modified GLP-1 analogues with a ureido residue replacement at position 2 were synthesized and showed preservation of agonist activity while exhibiting a substantial increase in stability. This enabling platform was applied to exenatide and lixisenatide analogues to generate two new ureidopeptides with antidiabetic properties and longer duration of action. Further analyses demonstrated that the improvement was due mainly to differences in signal bias and trafficking of the GLP-1 receptor. This study demonstrates the efficacy of single α-amino acid substitution with ureido residues to design long lasting peptides.
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.