ArticleACS chemical neuroscience2018
Inhibition of 14-3-3/Tau by Hybrid Small-Molecule Peptides Operating via Two Different Binding Modes.
Article in ACS chemical neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- In silico investigation of thiazole-semicarbazide hybrids as dual GSK-3β/Tau inhibitors for Alzheimer's disease.Scientific reports · 2026Article
- 14-3-3 Protein-Protein Interactions: From Mechanistic Understanding to Their Small-Molecule Stabilization.Chembiochem : a European journal of chemical biology · 2024Review
- The Development of CDC25A-Derived Phosphoseryl Peptides That Bind 14-3-3ε with High Affinities.International journal of molecular sciences · 2024Article
- Structure-Based Optimization of Covalent, Small-Molecule Stabilizers of the 14-3-3σ/ERα Protein-Protein Interaction from Nonselective Fragments.Journal of the American Chemical Society · 2023Article
- From Tethered to Freestanding Stabilizers of 14-3-3 Protein-Protein Interactions through Fragment Linking.Angewandte Chemie (International ed. in English) · 2023Article
- Insights into the Structural Conformations of the Tau Protein in Different Aggregation Status.Molecules (Basel, Switzerland) · 2023Review
- 14-3-3 Proteins are Potential Regulators of Liquid-Liquid Phase Separation.Cell biochemistry and biophysics · 2022Review
- Early increase of cerebrospinal fluid 14-3-3ζ protein in the alzheimer's disease continuum.Frontiers in aging neuroscience · 2022Article
- Contemporary biophysical approaches for studying 14-3-3 protein-protein interactions.Frontiers in molecular biosciences · 2022Review
- Cooperative stabilisation of 14-3-3σ protein-protein interactionsChemical science · 2021Article
- 14-3-3 Proteins: Novel Pharmacological Targets in Neurodegenerative Diseases.Trends in pharmacological sciences · 2021Review
- Strategies to expand peptide functionality through hybridisation with a small molecule component.RSC chemical biology · 2021Review
- NMR Studies of Tau Protein in Tauopathies.Frontiers in molecular biosciences · 2021Review
- A new soaking procedure for X-ray crystallographic structural determination of protein-peptide complexes.Acta crystallographica. Section F, Structural biology communications · 2020Article
- A Supramolecular Stabilizer of the 14-3-3ζ/ERα Protein-Protein Interaction with a Synergistic Mode of Action.Angewandte Chemie (International ed. in English) · 2020Article
- NMR Spectroscopy of supramolecular chemistry on protein surfaces.Beilstein journal of organic chemistry · 2020Review
- Potential Therapeutic Approaches to Alzheimer's Disease By Bioinformatics, Cheminformatics And Predicted Adme-Tox Tools.Current neuropharmacology · 2020Review
- Set-up and screening of a fragment library targeting the 14-3-3 protein interface.MedChemComm · 2019Article
- 14-3-3/Tau Interaction and Tau Amyloidogenesis.Journal of molecular neuroscience : MN · 2019Review
- Structure and Functions of Microtubule Associated Proteins Tau and MAP2c: Similarities and Differences.Biomolecules · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Current molecular hypotheses have not yet delivered marketable treatments for Alzheimer's disease (AD), arguably due to a lack of understanding of AD biology and an overreliance on conventional drug modalities. Protein-protein interactions (PPIs) are emerging drug targets, which show promise for the treatment of, e.g., cancer, but are still underexploited for treating neurodegenerative diseases. 14-3-3 binding to phosphorylated Tau is a promising PPI drug target based on its reported destabilizing effect on microtubules, leading to enhanced neurofibrillary tangle formation as a potential cause of AD-related neurodegeneration. Inhibition of 14-3-3/Tau may therefore be neuroprotective. Previously, we reported the structure-guided development of modified peptide inhibitors of 14-3-3/Tau. Here, we report further efforts to optimize the binding mode and activity of our modified Tau peptides through a combination of chemical synthesis, biochemical assays, and X-ray crystallography. Most notably, we were able to characterize two different high-affinity binding modes, both of which inhibited 14-3-3-binding to full-length PKA-phosphorylated Tau protein in vitro as measured by NMR spectroscopy. Our findings, besides producing useful tool inhibitor compounds for studying 14-3-3/Tau, have enhanced our understanding of the molecular parameters for inhibiting 14-3-3/Tau, which are important milestones toward the establishment of our 14-3-3 PPI hypothesis.
Indexed as
Identifiers
What OpenQuestion holds
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.