ArticleACS chemical neuroscience2022
A Small Molecule Stabilizes the Disordered Native State of the Alzheimer's Aβ Peptide.
Article in ACS chemical neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed.
- Transient Aggregation-Prone States in Disordered Proteins as Therapeutic Targets: The Amyloid-β Case.Journal of chemical information and modeling · 2026Article
- Tumor-derived branched-chain α-keto acids activate Notch signaling in tumor-associated macrophages to limit immunity.Nature immunology · 2026Article
- Transient tertiary structure in intrinsically disordered proteins revealed by multithermal enhanced sampling.Nature communications · 2026Article
- How small molecules stabilize oligomers of a phase-separating disordered protein.bioRxiv : the preprint server for biology · 2025Article
- Direct detection of an NH-π hydrogen bond in an intrinsically disordered peptide.Nature communications · 2025Article
- Determining accurate conformational ensembles of intrinsically disordered proteins at atomic resolution.Nature communications · 2025Article
- Ensemble Docking for Intrinsically Disordered Proteins.Journal of chemical information and modeling · 2025Article
- Covalent Adducts Formed by the Androgen Receptor Transactivation Domain and Small Molecule Drugs Remain Disordered.Journal of chemical information and modeling · 2025Article
- Atomistic molecular dynamics simulations of intrinsically disordered proteins.Current opinion in structural biology · 2025Review
- Evidence of α-Synuclein/Glucocerebrosidase Dual Targeting by Iminosugar Derivatives.ACS chemical neuroscience · 2025Article
- Ensemble docking for intrinsically disordered proteins.bioRxiv : the preprint server for biology · 2025Article
- Article
- Nitroxyl Hybrids with Curcumin and Stilbene Scaffolds Display Potent Antioxidant Activity, Remodel the Amyloid Beta Oligomer, and Reverse Amyloid Beta-Induced Cytotoxicity.Antioxidants (Basel, Switzerland) · 2024Article
- AlzDiscovery: A computational tool to identify Alzheimer's disease-causing missense mutations using protein structure information.Protein science : a publication of the Protein Society · 2024Article
- CoVAMPnet: Comparative Markov State Analysis for Studying Effects of Drug Candidates on Disordered Biomolecules.JACS Au · 2024Article
- Misfolded protein oligomers: mechanisms of formation, cytotoxic effects, and pharmacological approaches against protein misfolding diseases.Molecular neurodegeneration · 2024Review
- Folding-upon-binding pathways of an intrinsically disordered protein from a deep Markov state model.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Picosecond Dynamics of a Small Molecule in Its Bound State with an Intrinsically Disordered Protein.Journal of the American Chemical Society · 2024Article
- N-terminal domain of androgen receptor is a major therapeutic barrier and potential pharmacological target for treating castration resistant prostate cancer: a comprehensive review.Frontiers in pharmacology · 2024Review
- Conformational inhibitors of protein aggregation.Current opinion in structural biology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The stabilization of native states of proteins is a powerful drug discovery strategy. It is still unclear, however, whether this approach can be applied to intrinsically disordered proteins. Here, we report a small molecule that stabilizes the native state of the Aβ42 peptide, an intrinsically disordered protein fragment associated with Alzheimer's disease. We show that this stabilization takes place by a disordered binding mechanism, in which both the small molecule and the Aβ42 peptide remain disordered. This disordered binding mechanism involves enthalpically favorable local π-stacking interactions coupled with entropically advantageous global effects. These results indicate that small molecules can stabilize disordered proteins in their native states through transient non-specific interactions that provide enthalpic gain while simultaneously increasing the conformational entropy of the proteins.
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.