ArticleScientific reports2021
Defining the epitope of a blood-brain barrier crossing single domain antibody specific for the type 1 insulin-like growth factor receptor.
Article in Scientific reports, 2021. 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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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Antibody-Based Biologics for CNS Disorders.Antibodies (Basel, Switzerland) · 2026Review
- Pathology-directed drug delivery strategies: How to overcome blood-brain barrier for the treatment of brain diseases.Acta pharmaceutica Sinica. B · 2026Review
- Beyond the membrane: Internalization and compartmentalization of insulin‑like growth factor 1 receptor signaling in cancer pathogenesis and treatment (Review).International journal of oncology · 2026Review
- Bioconjugates for improved delivery of oligonucleotide therapeutics to the central nervous system.Advanced drug delivery reviews · 2026Review
- Immunoproteomics: The Evolution from Classical Methods to Emerging Techniques.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Epitope Screening by Hydrogen-Deuterium Exchange Mass Spectrometry for Improved Immunotherapeutic Outcomes.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Targeting vascular inflammation and endothelial dysfunction with nanobodies: emerging therapeutic strategies for cardiovascular disease.Frontiers in immunology · 2026Review
- Leveraging neonatal Fc receptor (FcRn) to enhance antibody transport across the blood brain barrier.Nature communications · 2025Article
- Nanobody engineering: computational modelling and design for biomedical and therapeutic applications.FEBS open bio · 2025Review
- Targeting Brain Drug Delivery with Macromolecules Through Receptor-Mediated Transcytosis.Pharmaceutics · 2025Review
- In vivo brain delivery of BBB-enabled iduronate 2-sulfatase in rats.Fluids and barriers of the CNS · 2025Article
- Receptor-mediated transcytosis for brain delivery of therapeutics: receptor classes and criteria.Frontiers in drug delivery · 2024Review
- Structure-based design of nanobodies that inhibit seeding of Alzheimer's patient-extracted tau fibrils.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Neuroprotective Effect of Wharton's Jelly-Derived Mesenchymal Stem Cell-Conditioned Medium (WJMSC-CM) on Diabetes-Associated Cognitive Impairment by Improving Oxidative Stress, Neuroinflammation, and Apoptosis.Stem cells international · 2023Article
- Hydrogen Deuterium Exchange and other Mass Spectrometry-based Approaches for Epitope Mapping.Frontiers in analytical science · 2023Article
- Brain Delivery of IGF1R5, a Single-Domain Antibody Targeting Insulin-like Growth Factor-1 Receptor.Pharmaceutics · 2022Article
- Article
- Transportation of Single-Domain Antibodies through the Blood-Brain Barrier.Biomolecules · 2021Review
- Article
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ligand-activated signaling through the type 1 insulin-like growth factor receptor (IGF1R) is implicated in many physiological processes ranging from normal human growth to cancer proliferation and metastasis. IGF1R has also emerged as a target for receptor-mediated transcytosis, a transport phenomenon that can be exploited to shuttle biotherapeutics across the blood-brain barrier (BBB). We employed differential hydrogen-deuterium exchange mass spectrometry (HDX-MS) and nuclear magnetic resonance (NMR) to characterize the interactions of the IGF1R ectodomain with a recently discovered BBB-crossing single-domain antibody (sdAb), VHH-IR5, in comparison with IGF-1 binding. HDX-MS confirmed that IGF-1 induced global conformational shifts in the L1/FnIII-1/-2 domains and α-CT helix of IGF1R. In contrast, the VHH-IR5 sdAb-mediated changes in conformational dynamics were limited to the α-CT helix and its immediate vicinity (L1 domain). High-resolution NMR spectroscopy titration data and linear peptide scanning demonstrated that VHH-IR5 has high-affinity binding interactions with a peptide sequence around the C-terminal region of the α-CT helix. Taken together, these results define a core linear epitope for VHH-IR5 within the α-CT helix, overlapping the IGF-1 binding site, and suggest a potential role for the α-CT helix in sdAb-mediated transcytosis.
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