ArticleProceedings of the National Academy of Sciences of the United States of America2025
Epitope-directed selection of GPCR nanobody ligands with evolvable function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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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
10 citing papers in PubMed.
- Discovery of an antagonist nanobody targeting the oxytocin receptor with tocolytic effect in mice.Nature communications · 2026Article
- Multivalent antibody-based conjugates as new tools for tailored modulation of G protein-coupled receptors.British journal of pharmacology · 2026Review
- Proteolysis activity mapping and substrate discovery platform for identifying tumor-activated biosensors.Nature chemical biology · 2026Article
- Nanobodies unlock new mechanisms to target G protein-coupled receptors.Molecular pharmacology · 2026Review
- Exploring the nanobody patent landscape: a focus on BCMA sequences and structural analysis.mAbs · 2025Article
- Nanobodies targeting hnRNPA2/B1 and tau.bioRxiv : the preprint server for biology · 2025Article
- Extracellular nanobody screening using conformationally stable GPCR variants.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Nanobody-drug conjugates for targeting specific GPCR pairs.PLoS biology · 2025Article
- Constitutively active orphan G protein-coupled receptors through the lenses of cryo-electron microscopy.The Journal of biological chemistry · 2025Review
- Progress toward new function and design of extracellular G protein-coupled receptor nanobodies.Molecular pharmacology · 2025Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Antibodies have the potential to target G protein-coupled receptors (GPCRs) with high receptor, cellular, and tissue selectivity; however, few antibody ligands for GPCRs exist. Here, we describe a generalizable selection method to enrich for GPCR ligands from a synthetic camelid antibody fragment (nanobody) library. Our strategy yielded multiple nanobody ligands for the angiotensin II type I receptor (AT1R), a prototypical GPCR and important drug target. We found that nanobodies readily act as allosteric modulators, encoding selectivity for both the receptor and chemical features of GPCR ligands. We then used structure-guided design to convert two nanobodies from allosteric ligands to competitive AT1R inhibitors through simple mutations. This work demonstrates that nanobodies can encode multiple pharmacological behaviors and have great potential as evolvable scaffolds for the development of next-generation GPCR therapeutics.
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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.