ArticleCommunications biology2021
Pharmacological inactivation of the prion protein by targeting a folding intermediate.
Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed.
- DreamFold: A World Model to efficiently generate protein folding pathways in the latent space.Protein science : a publication of the Protein Society · 2026Article
- Novel anti-prion compounds screening in prion-infected cell culture model combined with surface plasmon resonance analysis.Scientific reports · 2025Article
- Mapping cryptic phosphorylation sites in the human proteome.The EMBO journal · 2025Article
- G4 Oligonucleotide-Based Chaperones of Heterogeneous Nuclear Ribonucleoprotein A1.International journal of molecular sciences · 2025Article
- Mechanisms that matter: unbiased cellular screening for degraders.npj drug discovery · 2025Review
- Amyloid Forming Human Lysozyme Intermediates are Stabilized by Non-Native Amide-π Interactions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- The evolution of eukaryotic linear motifs governing the function of androgen receptor from fish to Homo sapiens.Nucleic acids research · 2025Article
- The physics-AI dialogue in drug design.RSC medicinal chemistry · 2025Review
- Prion protein promotes copper toxicity in Wilson disease.Nature communications · 2025Article
- New Therapeutic Modalities in Prion Diseases.Sub-cellular biochemistry · 2025Review
- Therapeutic Trajectories in Human Prion Diseases.Sub-cellular biochemistry · 2025Review
- Phase separation of microtubule-binding proteins - implications for neuronal function and disease.Journal of cell science · 2024Review
- Mechanistic analysis of Riboswitch Ligand interactions provides insights into pharmacological control over gene expression.Nature communications · 2024Article
- Discovery and Characterization of Two Folded Intermediates for Outer Membrane Protein TolC Biogenesis.Journal of molecular biology · 2024Article
- A Perspective on Interdicting in Protein Misfolding for Therapeutic Drug Design: Modulating the Formation of Nonlocal Contacts in α-Synuclein as a Strategy against Parkinson's Disease.The journal of physical chemistry. B · 2024Review
- Computational Docking as a Tool in Guiding the Drug Design of Rutaecarpine Derivatives as Potential SARS-CoV-2 Inhibitors.Molecules (Basel, Switzerland) · 2024Article
- It is theoretically possible to avoid misfolding into non-covalent lasso entanglements using small molecule drugs.PLoS computational biology · 2024Article
- Update on a brain-penetrant cardiac glycoside that can lower cellular prion protein levels in human and guinea pig paradigms.PloS one · 2024Article
- The neurotrophic activities of brain-derived neurotrophic factor are potentiated by binding with apigenin, a common flavone in vegetables, in stimulating the receptor signaling.CNS neuroscience & therapeutics · 2023Article
Corrections and comments
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Authors and funding
33 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent computational advancements in the simulation of biochemical processes allow investigating the mechanisms involved in protein regulation with realistic physics-based models, at an atomistic level of resolution. These techniques allowed us to design a drug discovery approach, named Pharmacological Protein Inactivation by Folding Intermediate Targeting (PPI-FIT), based on the rationale of negatively regulating protein levels by targeting folding intermediates. Here, PPI-FIT was tested for the first time on the cellular prion protein (PrP), a cell surface glycoprotein playing a key role in fatal and transmissible neurodegenerative pathologies known as prion diseases. We predicted the all-atom structure of an intermediate appearing along the folding pathway of PrP and identified four different small molecule ligands for this conformer, all capable of selectively lowering the load of the protein by promoting its degradation. Our data support the notion that the level of target proteins could be modulated by acting on their folding pathways, implying a previously unappreciated role for folding intermediates in the biological regulation of protein expression.
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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.