ArticleProceedings of the National Academy of Sciences of the United States of America2012
Structure-based design of conformation- and sequence-specific antibodies against amyloid β.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 134 citations in OpenAlex.
- Peptide-based therapeutics in the management of Alzheimer's disease (AD) and their potential to develop novel strategies.Metabolic brain disease · 2026Review
- A genetically encoded selection for amyloid-β oligomer binders.Nature chemical biology · 2025Article
- Experimental methods for studying amyloid cross-interactions.Protein science : a publication of the Protein Society · 2025Review
- Novel human recombinant N-acetylgalactosamine-6-sulfate sulfatase produced in a glyco-engineeredHeliyon · 2024Article
- M13 phage grafted with peptide motifs as a tool to detect amyloid-β oligomers in brain tissue.Communications biology · 2024Article
- Single-domain antibodies and aptamers drive new opportunities for neurodegenerative disease research.Frontiers in immunology · 2024Review
- Mechanisms and pathology of protein misfolding and aggregation.Nature reviews. Molecular cell biology · 2023Review
- Mechanistic Insight into Poly-Reactivity of Immune Antibodies upon Acid Denaturation or Arginine Mutation in Antigen-Binding Regions.Antibodies (Basel, Switzerland) · 2023Review
- 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
- Antibody-Mediated Clearance of Brain Amyloid-β: Mechanisms of Action, Effects of Natural and Monoclonal Anti-Aβ Antibodies, and Downstream Effects.Journal of Alzheimer's disease reports · 2023Review
- Fluorescent optotracers for bacterial and biofilm detection and diagnostics.Science and technology of advanced materials · 2023Review
- The Real-Time Validation of the Effectiveness of Third-Generation Hyperbranched Poly(ɛ-lysine) Dendrons-Modified KLVFF Sequences to Bind Amyloid-βSensors (Basel, Switzerland) · 2022Article
- Synthetic Pept-Ins as a Generic Amyloid-Like Aggregation-Based Platform forBioconjugate chemistry · 2021Article
- Contribution of the Commensal Microflora to the Immunological Homeostasis and the Importance of Immune-Related Drug Development for Clinical Applications.International journal of molecular sciences · 2021Review
- Plasmonic nanoparticle amyloid corona for screening Aβ oligomeric aggregate-degrading drugs.Nature communications · 2021Article
- Visualizing and trapping transient oligomers in amyloid assembly pathways.Biophysical chemistry · 2021Review
- An explicitly designed paratope of amyloid-β prevents neuronal apoptosisChemical science · 2020Article
- Local environment effects on charged mutations for developing aggregation-resistant monoclonal antibodies.Scientific reports · 2020Article
- How Does the Mono-Triazole Derivative Modulate AβACS omega · 2020Article
- Peptide-Based Molecular Strategies To Interfere with Protein Misfolding, Aggregation, and Cell Degeneration.Angewandte Chemie (International ed. in English) · 2020Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Conformation-specific antibodies that recognize aggregated proteins associated with several conformational disorders (e.g., Parkinson and prion diseases) are invaluable for diagnostic and therapeutic applications. However, no systematic strategy exists for generating conformation-specific antibodies that target linear sequence epitopes within misfolded proteins. Here we report a strategy for designing conformation- and sequence-specific antibodies against misfolded proteins that is inspired by the molecular interactions governing protein aggregation. We find that grafting small amyloidogenic peptides (6-10 residues) from the Aβ42 peptide associated with Alzheimer's disease into the complementarity determining regions of a domain (V(H)) antibody generates antibody variants that recognize Aβ soluble oligomers and amyloid fibrils with nanomolar affinity. We refer to these antibodies as gammabodies for grafted amyloid-motif antibodies. Gammabodies displaying the central amyloidogenic Aβ motif (18VFFA21) are reactive with Aβ fibrils, whereas those displaying the amyloidogenic C terminus (34LMVGGVVIA42) are reactive with Aβ fibrils and oligomers (and weakly reactive with Aβ monomers). Importantly, we find that the grafted motifs target the corresponding peptide segments within misfolded Aβ conformers. Aβ gammabodies fail to cross-react with other amyloidogenic proteins and scrambling their grafted sequences eliminates antibody reactivity. Finally, gammabodies that recognize Aβ soluble oligomers and fibrils also neutralize the toxicity of each Aβ conformer. We expect that our antibody design strategy is not limited to Aβ and can be used to readily generate gammabodies against other toxic misfolded proteins.
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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.