ArticlePloS one2014
A generic method for design of oligomer-specific antibodies.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 46 citations in OpenAlex.
- A genetically encoded selection for amyloid-β oligomer binders.Nature chemical biology · 2025Article
- Misfolded protein oligomers: mechanisms of formation, cytotoxic effects, and pharmacological approaches against protein misfolding diseases.Molecular neurodegeneration · 2024Review
- Nonpeptidic Oxazole-Based Prolyl Oligopeptidase Ligands with Disease-Modifying Effects on α-Synuclein Mouse Models of Parkinson's Disease.Journal of medicinal chemistry · 2023Article
- Plasma IAPP-Autoantibody Levels in Alzheimer's Disease Patients Are Affected byInternational journal of molecular sciences · 2023Article
- Monitoring α-synuclein aggregation.Neurobiology of disease · 2023Review
- Diagnostic value of skin RT-QuIC in Parkinson's disease: a two-laboratory study.NPJ Parkinson's disease · 2021Article
- Novel multivalent design of a monoclonal antibody improves binding strength to soluble aggregates of amyloid beta.Translational neurodegeneration · 2021Article
- Alpha-synuclein research: defining strategic moves in the battle against Parkinson's disease.NPJ Parkinson's disease · 2021Review
- Age-related increase of alpha-synuclein oligomers is associated with motor disturbances in L61 transgenic mice.Neurobiology of aging · 2021Article
- Kinetic fingerprints differentiate the mechanisms of action of anti-Aβ antibodies.Nature structural & molecular biology · 2020Article
- Nature-inspired design and evolution of anti-amyloid antibodies.The Journal of biological chemistry · 2019Article
- Efficient RT-QuIC seeding activity for α-synuclein in olfactory mucosa samples of patients with Parkinson's disease and multiple system atrophy.Translational neurodegeneration · 2019Article
- Structural and kinetic basis for the selectivity of aducanumab for aggregated forms of amyloid-β.Scientific reports · 2018Article
- Article
- Phage display and kinetic selection of antibodies that specifically inhibit amyloid self-replication.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Human Neural Progenitor Transplantation Rescues Behavior and Reduces α-Synuclein in a Transgenic Model of Dementia with Lewy Bodies.Stem cells translational medicine · 2017Article
- The role of histidines in amyloid β fibril assembly.FEBS letters · 2017Article
- Inhibition of Prolyl Oligopeptidase Restores Spontaneous Motor Behavior in the α-Synuclein Virus Vector-Based Parkinson's Disease Mouse Model by Decreasing α-Synuclein Oligomeric Species in Mouse Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Aberrant Collagen Composition of the Trabecular Meshwork Results in Reduced Aqueous Humor Drainage and Elevated IOP in MMP-9 Null Mice.Investigative ophthalmology & visual science · 2016Article
- Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibodies that preferentially and specifically target pathological oligomeric protein and peptide assemblies, as opposed to their monomeric and amyloid counterparts, provide therapeutic and diagnostic opportunities for protein misfolding diseases. Unfortunately, the molecular properties associated with oligomer-specific antibodies are not well understood, and this limits targeted design and development. We present here a generic method that enables the design and optimisation of oligomer-specific antibodies. The method takes a two-step approach where discrimination between oligomers and fibrils is first accomplished through identification of cryptic epitopes exclusively buried within the structure of the fibrillar form. The second step discriminates between monomers and oligomers based on differences in avidity. We show here that a simple divalent mode of interaction, as within e.g. the IgG isotype, can increase the binding strength of the antibody up to 1500 times compared to its monovalent counterpart. We expose how the ability to bind oligomers is affected by the monovalent affinity and the turnover rate of the binding and, importantly, also how oligomer specificity is only valid within a specific concentration range. We provide an example of the method by creating and characterising a spectrum of different monoclonal antibodies against both the Aβ peptide and α-synuclein that are associated with Alzheimer's and Parkinson's diseases, respectively. The approach is however generic, does not require identification of oligomer-specific architectures, and is, in essence, applicable to all polypeptides that form oligomeric and fibrillar assemblies.
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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.