ArticleJournal of the American Chemical Society2012
Dependence of avidity on linker length for a bivalent ligand-bivalent receptor model system.
Article in Journal of the American Chemical Society, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Development of an ultrahigh affinity, trimeric ACE2 biologic as a universal SARS-CoV-2 antagonist.Communications biology · 2025Article
- Avidity-based bright and photostable light-up aptamers for single-molecule mRNA imaging.Nature chemical biology · 2023Article
- A bivalent remipede toxin promotes calcium release via ryanodine receptor activation.Nature communications · 2023Article
- ScrepYard: An online resource for disulfide-stabilized tandem repeat peptides.Protein science : a publication of the Protein Society · 2023Article
- Synthesis, Biological Evaluation, and Molecular Dynamics of Carbothioamides Derivatives as Carbonic Anhydrase II and 15-Lipoxygenase Inhibitors.Molecules (Basel, Switzerland) · 2022Article
- Exploring divalent conjugates of 5-RSC advances · 2022Article
- Mapping the binding site topology of amyloid protein aggregates using multivalent ligands.Chemical science · 2021Article
- Nanoscale spatial dependence of avidity in an IgG1 antibody.Scientific reports · 2021Article
- PEG Linker Length Strongly Affects Tumor Cell Killing by PEGylated Carbonic Anhydrase Inhibitors in Hypoxic Carcinomas Expressing Carbonic Anhydrase IX.International journal of molecular sciences · 2021Article
- Two for the Price of One: Heterobivalent Ligand Design Targeting Two Binding Sites on Voltage-Gated Sodium Channels Slows Ligand Dissociation and Enhances Potency.Journal of medicinal chemistry · 2020Article
- Intrinsically disordered linkers control tethered kinases via effective concentration.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Interaction between the scaffold proteins CBP by IQGAP1 provides an interface between gene expression and cytoskeletal activity.Scientific reports · 2020Article
- The CD28 Transmembrane Domain Contains an Essential Dimerization Motif.Frontiers in immunology · 2020Article
- Effective concentrations enforced by intrinsically disordered linkers are governed by polymer physics.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Assembly of Divalent Ligands and Their Effect on Divalent Binding to Pseudomonas aeruginosa Lectin LecA.The Journal of organic chemistry · 2019Article
- The size matters? A computational tool to design bivalent ligands.Bioinformatics (Oxford, England) · 2018Article
- Article
- A general model for predicting the binding affinity of reversibly and irreversibly dimerized ligands.PloS one · 2017Article
- In Vivo Efficacy of Measles Virus Fusion Protein-Derived Peptides Is Modulated by the Properties of Self-Assembly and Membrane Residence.Journal of virology · 2017Article
- Mix and match recognition modules for the formation of H-bonded duplexes.Chemical science · 2016Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
This paper describes a synthetic dimer of carbonic anhydrase, and a series of bivalent sulfonamide ligands with different lengths (25 to 69 Å between the ends of the fully extended ligands), as a model system to use in examining the binding of bivalent antibodies to antigens. Assays based on analytical ultracentrifugation and fluorescence binding indicate that this system forms cyclic, noncovalent complexes with a stoichiometry of one bivalent ligand to one dimer. This dimer binds the series of bivalent ligands with low picomolar avidities (K(d)(avidity) = 3-40 pM). A structurally analogous monovalent ligand binds to one active site of the dimer with K(d)(mono) = 16 nM. The bivalent association is thus significantly stronger (K(d)(mono)/K(d)(avidity) ranging from ~500 to 5000 unitless) than the monovalent association. We infer from these results, and by comparison of these results to previous studies, that bivalency in antibodies can lead to associations much tighter than monovalent associations (although the observed bivalent association is much weaker than predicted from the simplest level of theory: predicted K(d)(avidity) of ~0.002 pM and K(d)(mono)/K(d)(avidity) ~ 8 × 10(6) unitless).
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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.