ArticleJournal of medicinal chemistry2019
Binding of Monovalent and Bivalent Ligands by Transthyretin Causes Different Short- and Long-Distance Conformational Changes.
Article in Journal of medicinal chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Induced Circular Dichroism From the Binding of Achiral Bivalent Ligands to Transthyretin.Journal of molecular recognition : JMR · 2026Article
- Exploring Tafamidis Effects Through PBPK-QSP Modelling.Pharmaceutics · 2026Article
- Phenomenological model of transthyretin stabilization.Scientific reports · 2026Article
- Mechanism of inhibition of acid-mediated transthyretin aggregation by designed peptides.The Journal of biological chemistry · 2025Article
- Design and Mechanistic Analysis of a Potent Bivalent Inhibitor of Transthyretin Amyloid Fibrillogenesis.Journal of medicinal chemistry · 2025Article
- Differential Binding Affinities and Kinetics of Transthyretin Stabilizers.Journal of cardiovascular pharmacology · 2025Article
- A Comprehensive Review on Chemistry and Biology of Tafamidis in Transthyretin Amyloidosis.Mini reviews in medicinal chemistry · 2024Review
- Parameter estimation and identifiability analysis for a bivalent analyte model of monoclonal antibody-antigen binding.Analytical biochemistry · 2023Article
- Transthyretin Binding Mode Dichotomy of FluorescentACS chemical neuroscience · 2023Article
- Targeted treatments of AL and ATTR amyloidosis.Heart failure reviews · 2022Review
- Calcium Binds to Transthyretin with Low Affinity.Biomolecules · 2022Article
- Distinct dissociation rates of murine and human norovirus P-domain dimers suggest a role of dimer stability in virus-host interactions.Communications biology · 2022Article
- Treatment of Transthyretin Amyloid Cardiomyopathy: The Current Options, the Future, and the Challenges.Journal of clinical medicine · 2022Review
- The Transthyretin/Oleuropein Aglycone Complex: A New Tool against TTR Amyloidosis.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Amyloid Formation by Globular Proteins: The Need to Narrow the Gap BetweenFrontiers in molecular biosciences · 2022Review
- Current and Emerging Therapies for Hereditary Transthyretin Amyloidosis: Strides Towards a Brighter Future.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Transthyretin Misfolding, A Fatal Structural Pathogenesis Mechanism.International journal of molecular sciences · 2021Review
- Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis.International journal of molecular sciences · 2021Article
- Preparative Scale Production of Recombinant Human Transthyretin for Biophysical Studies of Protein-Ligand and Protein-Protein Interactions.International journal of molecular sciences · 2020Article
- Rational Design, Synthesis, Characterization and Evaluation of Iodinated 4,4'-Bipyridines as New Transthyretin Fibrillogenesis Inhibitors.Molecules (Basel, Switzerland) · 2020Article
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
The wild type protein, transthyretin (TTR), and over 120 genetic TTR variants are amyloidogenic and cause, respectively, sporadic and hereditary systemic TTR amyloidosis. The homotetrameric TTR contains two identical thyroxine binding pockets, occupation of which by specific ligands can inhibit TTR amyloidogenesis in vitro. Ligand binding stabilizes the tetramer, inhibiting its proteolytic cleavage and its dissociation. Here, we show with solution-state NMR that ligand binding induces long-distance conformational changes in the TTR that have not previously been detected by X-ray crystallography, consistently with the inhibition of the cleavage of the DE loop. The NMR findings, coupled with surface plasmon resonance measurements, have identified dynamic exchange processes underlying the negative cooperativity of binding of "monovalent" ligand tafamidis. In contrast, mds84, our prototypic "bivalent" ligand, which is a more potent stabilizer of TTR in vitro that occupies both thyroxine pockets and the intramolecular channel between them, has greater structural effects.
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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.