ArticleACS chemical biology2016
Backbone Modification of a Parathyroid Hormone Receptor-1 Antagonist/Inverse Agonist.
Article in ACS chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- Expanding the Chemical Space of Mechanically Interlocked Peptides (MIPs) via Rational Design and Metabolite Profiling.JACS Au · 2025Article
- A Computational Perspective to Intermolecular Interactions and the Role of the Solvent on Regulating Protein Properties.Chemical reviews · 2025Review
- Advances in Peptidomimetics for Next-Generation Therapeutics: Strategies, Modifications, and Applications.Chemical reviews · 2025Review
- Advance in peptide-based drug development: delivery platforms, therapeutics and vaccines.Signal transduction and targeted therapy · 2025Review
- Structural information in therapeutic peptides: Emerging applications in biomedicine.FEBS open bio · 2025Review
- Ultrashort-Peptide-Responsive Gene Switches for Regulation of Therapeutic Protein Expression in Mammalian Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Highly biased agonism for GPCR ligands via nanobody tethering.Nature communications · 2024Article
- Backbone Modification Provides a Long-Acting Inverse Agonist of Pathogenic, Constitutively Active PTH1R Variants.Journal of the American Chemical Society · 2024Article
- Exploring FDA-Approved Frontiers: Insights into Natural and Engineered Peptide Analogues in the GLP-1, GIP, GHRH, CCK, ACTH, and α-MSH Realms.Biomolecules · 2024Review
- New Insights into the Structure and Function of Class B1 GPCRs.Endocrine reviews · 2023Article
- Strategies to improve the physicochemical properties of peptide-based drugs.Pharmaceutical research · 2023Review
- Backbone distortions in lactam-bridged helical peptides.Journal of peptide science : an official publication of the European Peptide Society · 2022Article
- Actions of Parathyroid Hormone Ligand Analogues in Humanized PTH1R Knockin Mice.Endocrinology · 2022Article
- Rational Discovery of Antiviral Whey Protein-Derived Small Peptides Targeting the SARS-CoV-2 Main Protease.Biomedicines · 2022Article
- Therapeutic peptides: current applications and future directions.Signal transduction and targeted therapy · 2022Review
- Activity-based, bioorthogonal imaging of phospholipase D reveals spatiotemporal dynamics of GPCR-Gq signaling.Cell chemical biology · 2022Article
- Molecular insights into differentiated ligand recognition of the human parathyroid hormone receptor 2.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- PTH/PTHrP Receptor Signaling, Allostery, and Structures.Trends in endocrinology and metabolism: TEM · 2019Review
- Progression of Mineral Ion Abnormalities in Patients With Jansen Metaphyseal Chondrodysplasia.The Journal of clinical endocrinology and metabolism · 2018Article
- Development of Potent, Protease-Resistant Agonists of the Parathyroid Hormone Receptor with Broad β Residue Distribution.Journal of medicinal chemistry · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
A backbone-modified peptide derived from parathyroid hormone (PTH) is shown to function as an inhibitor and inverse agonist of parathyroid hormone receptor-1 (PTHR1) signaling. This receptor acts to regulate calcium and phosphate homeostasis, as well as bone turnover and development. PTH is a natural agonist of PTHR1, and PTH(1-34) displays full activity relative to the natural 84-residue hormone. PTH(1-34) is used clinically to treat osteoporosis. N-terminally truncated derivatives of PTH(1-34), such as PTH(7-34), are known to bind to PTHR1 without initiating intracellular signaling and can thus act as competitive antagonists of PTH-induced signaling at PTHR1. In some cases, N-terminally truncated PTH derivatives also act as inverse agonists of PTHR1 variants that display pathologically high levels of signaling in the absence of PTH. Many analogues of PTH, however, are rapidly degraded by proteases, which may limit biomedical application. We show that backbone modification via periodic replacement of α-amino acid residues with homologous β-amino acid residues leads to an α/β-PTH(7-34) peptide that retains the antagonist and inverse agonist activities of the prototype α-peptide while exhibiting enhanced stability in the presence of aggressive proteases. These findings highlight the value of backbone-modified peptides derived from PTH as tools for investigating determinants of PTH metabolism and provide guidance for designing therapeutic agents for diseases arising from excessive ligand-dependent or ligand-independent PTHR1 activity.
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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.