ArticleNature communications2022
Tuning the rate of aggregation of hIAPP into amyloid using small-molecule modulators of assembly.
Article in Nature communications, 2022. 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, 70 citations in OpenAlex.
- Impact of Stabilizing Osmolytes on the Conformational Dynamics of Human and Rat Islet Amyloid Polypeptides.Proteins · 2026Article
- Fine-Tuning hIAPP Amyloidogenesis: Probing Molecular Mechanisms via Fluorinated Core Substitutions.ACS bio & med chem Au · 2026Article
- QBP1 Peptide as a Potential Anti-Amyloidogenic Therapy for Type 2 Diabetes: An In Vitro Study.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Rapid elongation drives the exceptionally fast aggregation of the most common localized human amyloid medin.Communications chemistry · 2026Article
- A Highly Sensitive Water-Soluble Donor-Acceptor Dye for Early-Stage Amyloid Aggregation Kinetics.The journal of physical chemistry. B · 2026Article
- Massively parallel quantification of mutational impact on IAPP amyloid formation.Nature communications · 2026Article
- How small molecules stabilize oligomers of a phase-separating disordered protein.bioRxiv : the preprint server for biology · 2025Article
- Inhibition of Human Amylin Aggregation:ACS omega · 2025Article
- O-glycosylated peptides curtail the aggregation and toxicity of human islet amyloid polypeptide.Communications biology · 2025Article
- Experimental and computational analysis of the basis for accelerated amyloid formation by a disease linked mutant of human islet amyloid polypeptide.Protein science : a publication of the Protein Society · 2025Article
- Article
- Monomer binding modes of small molecules that modulate the kinetics of hIAPP amyloid formation.bioRxiv : the preprint server for biology · 2025Article
- Employing deep mutational scanning in theProceedings of the National Academy of Sciences of the United States of America · 2025Article
- DIRseq: a method for predicting drug-interacting residues of intrinsically disordered proteins from sequences.bioRxiv : the preprint server for biology · 2025Article
- Peptidomimetics Targeting the Amyloidogenicity of Nucleophosmin 1 Mutations in Acute Myeloid Leukemia.Chembiochem : a European journal of chemical biology · 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
- Kinetic Steering of Amyloid Formation and Polymorphism by Canagliflozin, a Type-2 Diabetes Drug.Journal of the American Chemical Society · 2025Article
- Rapid discovery of cyclic peptide protein aggregation inhibitors by continuous selection.Nature chemical biology · 2025Article
- Ensemble docking for intrinsically disordered proteins.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Human islet amyloid polypeptide (hIAPP) self-assembles into amyloid fibrils which deposit in pancreatic islets of type 2 diabetes (T2D) patients. Here, we applied chemical kinetics to study the mechanism of amyloid assembly of wild-type hIAPP and its more amyloidogenic natural variant S20G. We show that the aggregation of both peptides involves primary nucleation, secondary nucleation and elongation. We also report the discovery of two structurally distinct small-molecule modulators of hIAPP assembly, one delaying the aggregation of wt hIAPP, but not S20G; while the other enhances the rate of aggregation of both variants at substoichiometric concentrations. Investigation into the inhibition mechanism(s) using chemical kinetics, native mass spectrometry, fluorescence titration, SPR and NMR revealed that the inhibitor retards primary nucleation, secondary nucleation and elongation, by binding peptide monomers. By contrast, the accelerator predominantly interacts with species formed in the lag phase. These compounds represent useful chemical tools to study hIAPP aggregation and may serve as promising starting-points for the development of therapeutics for T2D.
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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.