ReviewBritish journal of pharmacology2013
Exploring avidity: understanding the potential gains in functional affinity and target residence time of bivalent and heterobivalent ligands.
Review in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers, 1 of them a synthesis that pooled it.
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Who cites it
146 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Live long and active: Polypeptide-mediated assembly of antibody variable fragments.Advanced drug delivery reviews · 2020Pooled it
- Structure-informed theoretical modeling defines principles governing avidity in bivalent protein interactions.The Journal of biological chemistry · 2026Article
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- Comparative analysis of anti-MICA scFv affinities: Insights from three label-free biophysical methods and biological validation.Biotechnology reports (Amsterdam, Netherlands) · 2026Article
- In Vivo Auto-tuning of Antibody-Drug Conjugate Delivery to Maximize Efficacy Using High-Avidity, Low-Affinity Antibodies.Molecular cancer therapeutics · 2026Article
- Mapping SARS-CoV-2 Nucleocapsid Function with Nanobodies.bioRxiv : the preprint server for biology · 2026Article
- Targeting Folate Receptors for the Detection and Selective Treatment of Cancer: Advanced Precision Oncology in Practice.International journal of biological sciences · 2026Review
- Review
- The Constrained Disorder Principle: A Paradigm Shift for Accurate Interactome Mapping and Information Analysis in Complex Biological Systems.Bioengineering (Basel, Switzerland) · 2025Review
- VesicleVoyager: In Vivo Selection of Surface Displayed Proteins That Direct Extracellular Vesicles to Tissue-Specific Targets.Journal of extracellular vesicles · 2025Article
- An Asymptotic Analysis of Bivalent Monoclonal Antibody-Antigen Binding.Bulletin of mathematical biology · 2025Article
- A New Approach to Examine Cell-Antibody Avidity with Surface Plasmon Resonance Imaging.Biosensors · 2025Article
- Scaffold-hopping for molecular glues targeting the 14-3-3/ERα complex.Nature communications · 2025Article
- Dimeric DNA Aptamers for the Spike Protein of SARS-CoV-2 Derived from a Structured Library with Dual Random Domains.Small methods · 2025Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- DNA origami signal amplification in lateral flow immunoassays.Nature communications · 2025Article
- Article
- DNA Aptamer-Polymer Conjugates for Selective Targeting of Integrin α4β1ACS applied materials & interfaces · 2025Article
- A shorter linker in the bispecific antibody RmAb158-scFv8D3 improves TfR-mediated blood-brain barrier transcytosis in vitro.Scientific reports · 2024Article
86 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bivalent ligands are increasingly important therapeutic agents. Although the naturally occurring antibodies are predominant, it is becoming more common to combine different antibody fragments or even low molecular weight compounds to generate heterobivalent ligands. Such ligands exhibit markedly increased affinity (i.e. avidity) and target residence time when both pharmacophores can bind simultaneously to their target sites. This is because binding of one pharmacophore forces the second tethered one to stay close to its corresponding site. This 'forced proximity' favours its binding and rebinding (once dissociated) to that site. However, rebinding will also take place when the diffusion of freshly dissociated ligands is merely slowed down. The present differential equation-based simulations explore the way both situations affect ligand binding. Both delay the attainment of binding equilibrium (resulting in steep saturation curves) and also increase the target residence time. Competitive ligands are able to interfere in a concentration-dependent manner, although much higher concentrations are required in the 'forced proximity' situation. Also, it is only in that situation that the ligand shows increased affinity. These simulations shed light on two practical consequences. Depending on the pharmacokinetic half-life of the bivalent ligand in the body, it may not have sufficient time to achieve equilibrium with the target. This will result in lower potency than expected, although it would have significant advantages in terms of residence time. In in vitro experiments, the manifestation of steep saturation curves and of accelerated dissociation in the presence of competitive ligands could mistakenly be interpreted as evidence for non-competitive, allosteric interactions.
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