ArticleProceedings of the National Academy of Sciences of the United States of America2016
Engineering a long-acting, potent GLP-1 analog for microstructure-based transdermal delivery.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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
19 citing papers in PubMed.
- Microneedle-Assisted Delivery of Biologics: From Large Molecules to Cancer Vaccines.AAPS PharmSciTech · 2026Review
- Isothiourea-Catalysed Acylative Kinetic and Dynamic Kinetic Resolution of Planar Chiral Paracyclophanols.Angewandte Chemie (International ed. in English) · 2025Article
- Design and Biosynthesis of Ornithine 8-Containing Semaglutide Variants with a Click Chemistry-Modifiable Position 26.ACS synthetic biology · 2025Article
- A Closer Look at the Dermatological Profile of GLP-1 Agonists.Diseases (Basel, Switzerland) · 2025Review
- Fabrication and Preclinical Evaluation of Hyaluronic Acid/Aminoclay Nanocomposite Microneedles for Noninvasive Delivery of Semaglutide in Anti-Obesity Therapy.International journal of nanomedicine · 2025Article
- Fatty Acid Derivatization and Cyclization of the Immunomodulatory Peptide RP-182 Targeting CD206high Macrophages Improve Antitumor Activity.Molecular cancer therapeutics · 2024Article
- Unnatural helical peptidic foldamers as protein segment mimics.Chemical Society reviews · 2023Review
- Article
- Integrated investigation and experimental validation of PPARG as an oncogenic driver: implications for prognostic assessment and therapeutic targeting in hepatocellular carcinoma.Frontiers in pharmacology · 2023Article
- α/Sulfono-γ-AApeptide Hybrid Analogues of Glucagon with Enhanced Stability and Prolonged In Vivo Activity.Journal of medicinal chemistry · 2021Article
- Insights Into the Structure-Function Relationships of Dimeric C3d Fragments.Frontiers in immunology · 2021Article
- Hydrocarbon-Stitched Peptide Agonists of Glucagon-Like Peptide-1 Receptor.ACS chemical biology · 2020Article
- Recombinant Expression and Stapling of a Novel Long-Acting GLP-1R Peptide Agonist.Molecules (Basel, Switzerland) · 2020Article
- Modelling the intradermal delivery of microneedle array patches for long-acting antiretrovirals using PBPK.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2019Article
- Design of a Long-Acting and Selective MEG-Fatty Acid Stapled Prolactin-Releasing Peptide Analog.ACS medicinal chemistry letters · 2019Article
- Design of Stapled Oxyntomodulin Analogs Containing Functionalized Biphenyl Cross-Linkers.Tetrahedron · 2019Article
- Polymeric microneedles for transdermal protein delivery.Advanced drug delivery reviews · 2018Review
- Protein Crosslinking by Genetically Encoded Noncanonical Amino Acids with Reactive Aryl Carbamate Side Chains.Angewandte Chemie (International ed. in English) · 2017Article
- A Helix-Stabilizing Linker Improves Subcutaneous Bioavailability of a Helical Peptide Independent of Linker Lipophilicity.Bioconjugate chemistry · 2016Article
Corrections and comments
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antidiabetic treatments aiming to reduce body weight are currently gaining increased interest. Exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist administered twice daily via s.c. injection, improves glycemic control, often with associated weight reduction. To further improve the therapeutic efficacy of exendin-4, we have developed a novel peptide engineering strategy that incorporates a serum protein binding motif onto a covalent side-chain staple and applied to the peptide to enhance its helicity and, as a consequence, its potency and serum half-life. We demonstrated that one of the resulting peptides, E6, has significantly improved half-life and glucose tolerance in an oral glucose tolerance test in rodents. Chronic treatment of E6 significantly decreased body weight and fasting blood glucose, improved lipid metabolism, and also reduced hepatic steatosis in diet-induced obese mice. Moreover, the high potency of E6 allowed us to administer this peptide using a dissolvable microstructure-based transdermal delivery system. Pharmacokinetic and pharmacodynamic studies in guinea pigs showed that a single 5-min application of a microstructure system containing E6 significantly improved glucose tolerance for 96 h. This delivery strategy may offer an effective and patient-friendly alternative to currently marketed GLP-1 injectables and can likely be extended to other peptide hormones.
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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.