ArticleNature communications2024
Highly biased agonism for GPCR ligands via nanobody tethering.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- Mechanistic trade-offs between local and long-range signaling activity in natural and synthetic morphogens.Science advances · 2026Article
- Antigen-Detected NMR for Minimal Epitope Engineering and Structure-Guided Selection of a NaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mechanisms and Manifestations of Ligand Bias in Signaling: Focus on Receptor Tyrosine Kinases.Chemical reviews · 2026Review
- Multivalent antibody-based conjugates as new tools for tailored modulation of G protein-coupled receptors.British journal of pharmacology · 2026Review
- Selective positive allosteric modulation of βNature communications · 2026Article
- Nanobodies unlock new mechanisms to target G protein-coupled receptors.Molecular pharmacology · 2026Review
- Nanobody-Based Bioconjugates as Potent and Broadly Active Inhibitors of HIV Entry.Journal of the American Chemical Society · 2026Article
- Article
- Elucidating biased signaling in class A GPCRs.Trends in pharmacological sciences · 2025Review
- Article
- Nanobody-drug conjugates for targeting specific GPCR pairs.PLoS biology · 2025Article
- Development of bitopic nanobody-ligand conjugates targeting G protein-coupled receptors and exhibiting logic-gated signaling.PLoS biology · 2025Article
- Bitopic AJournal of medicinal chemistry · 2025Article
- Biased signalingActa pharmaceutica Sinica. B · 2025Review
- Progress toward new function and design of extracellular G protein-coupled receptor nanobodies.Molecular pharmacology · 2025Review
- Development of Mutant MBiochemistry · 2025Article
- Evaluation of AlphaFold modeling for elucidation of nanobody-peptide epitope interactions.The Journal of biological chemistry · 2025Article
- Induced proximity at the cell surface.Nature biotechnology · 2025Review
- Generation of Site-Specifically Labeled Affinity Reagents via Use of a Self-Labeling Single Domain Antibody.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Evaluation of Alphafold modeling for elucidation of nanobody-peptide epitope interactions.bioRxiv : the preprint server for biology · 2025Article
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4 authors.
Funding
Abstract
Ligand-induced activation of G protein-coupled receptors (GPCRs) can initiate signaling through multiple distinct pathways with differing biological and physiological outcomes. There is intense interest in understanding how variation in GPCR ligand structure can be used to promote pathway selective signaling ("biased agonism") with the goal of promoting desirable responses and avoiding deleterious side effects. Here we present an approach in which a conventional peptide ligand for the type 1 parathyroid hormone receptor (PTHR1) is converted from an agonist which induces signaling through all relevant pathways to a compound that is highly selective for a single pathway. This is achieved not through variation in the core structure of the agonist, but rather by linking it to a nanobody tethering agent that binds with high affinity to a separate site on the receptor not involved in signal transduction. The resulting conjugate represents the most biased agonist of PTHR1 reported to date. This approach holds promise for facile generation of pathway selective ligands for other GPCRs.
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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 Socratic graph.