ArticleJournal of the American Chemical Society2011
Lysine-specific molecular tweezers are broad-spectrum inhibitors of assembly and toxicity of amyloid proteins.
Article in Journal of the American Chemical Society, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 papers.
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Who cites it
127 citing papers in PubMed, 293 citations in OpenAlex.
- Bridging stimulus-responsive and dissipative peptide assemblies to build complex interactive biomaterials.Nature reviews. Chemistry · 2026Review
- Prion Protein-Derived Cell-Penetrating Peptide Inhibits Type II Diabetes-Associated Islet Amyloid Polypeptide Aggregation and Cytotoxicity.Biochemistry · 2026Article
- Allosteric Modulation of Pathological Ataxin-3 Aggregation: A Path to Spinocerebellar Ataxia Type-3 Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Advanced Molecular Tweezers Effectively Target Membranes Lacking Choline Headgroups for Broad-Spectrum Antiviral Efficacy.Journal of the American Chemical Society · 2026Article
- Nanomolar Affinity Host-Dye Reporter Pairs from Fluorescently Labeled Oligoarginine Peptides and p-Sulfonatocalix[4]arene.Chembiochem : a European journal of chemical biology · 2026Article
- Antimicrobial Peptides as Cross-Seeding Modulators at the Neurodegenerative-Infectious Interface.Research (Washington, D.C.) · 2026Review
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Identification of small molecule dimethyoxyphenyl piperazine inhibitors of alpha-synuclein fibril growth.Scientific reports · 2025Article
- Light-Triggered Disassembly of Peptide Nanostructures.Chembiochem : a European journal of chemical biology · 2025Article
- Lysine-Targeting Inhibitors of Amyloidogenic Protein Aggregation: A Promise for Neurodegenerative Proteinopathies.JACS Au · 2025Review
- Modular protein frameworks via supramolecular synthons.Biophysical reviews · 2025Review
- Mass spectrometry structural analysis of intrinsically disordered phosphoproteins.International journal of mass spectrometry · 2025Article
- Leveraging heterocycle-fused 1,4-benzoquinone to design chemical modulators for both metal-free and metal-bound amyloid-β.Chemical science · 2025Article
- Dual modulation of amyloid beta and tau aggregation and dissociation in Alzheimer's disease: a comprehensive review of the characteristics and therapeutic strategies.Translational neurodegeneration · 2025Review
- N-Terminal Protein Binding and Disorder-to-Order Transition by a Synthetic Receptor.Biochemistry · 2025Article
- Small Molecules, α-Synuclein Pathology, and the Search for Effective Treatments in Parkinson's Disease.International journal of molecular sciences · 2024Review
- Pathological Involvement of Protein Phase Separation and Aggregation in Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Tryptanthrin Analogs Substoichiometrically Inhibit Seeded and Unseeded Tau4RD Aggregation.bioRxiv : the preprint server for biology · 2024Article
- Nanotechnology for microglial targeting and inhibition of neuroinflammation underlying Alzheimer's pathology.Translational neurodegeneration · 2024Article
- Protein aggregation and therapeutic strategies in SOD1- and TDP-43- linked ALS.Frontiers in molecular biosciences · 2024Review
67 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
Abstract
Amyloidoses are diseases characterized by abnormal protein folding and self-assembly, for which no cure is available. Inhibition or modulation of abnormal protein self-assembly, therefore, is an attractive strategy for prevention and treatment of amyloidoses. We examined Lys-specific molecular tweezers and discovered a lead compound termed CLR01, which is capable of inhibiting the aggregation and toxicity of multiple amyloidogenic proteins by binding to Lys residues and disrupting hydrophobic and electrostatic interactions important for nucleation, oligomerization, and fibril elongation. Importantly, CLR01 shows no toxicity at concentrations substantially higher than those needed for inhibition. We used amyloid β-protein (Aβ) to further explore the binding site(s) of CLR01 and the impact of its binding on the assembly process. Mass spectrometry and solution-state NMR demonstrated binding of CLR01 to the Lys residues in Aβ at the earliest stages of assembly. The resulting complexes were indistinguishable in size and morphology from Aβ oligomers but were nontoxic and were not recognized by the oligomer-specific antibody A11. Thus, CLR01 binds already at the monomer stage and modulates the assembly reaction into formation of nontoxic structures. The data suggest that molecular tweezers are unique, process-specific inhibitors of aberrant protein aggregation and toxicity, which hold promise for developing disease-modifying therapy for amyloidoses.
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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.