ArticleJournal of diabetes research2015
Charge-Based Inhibitors of Amylin Fibrillization and Toxicity.
Article in Journal of diabetes research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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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.
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Who cites it
10 citing papers in PubMed.
- Synthetic deformylated α-helical PSMα3 as a selective inhibitor of human amyloid aggregation.Scientific reports · 2025Article
- Plant Hormone Cytokinin as Aggregation Modulator of Gelsolin Amyloidosis.Journal of peptide science : an official publication of the European Peptide Society · 2025Article
- Human islet amyloid polypeptide: A therapeutic target for the management of type 2 diabetes mellitus.Journal of pharmaceutical analysis · 2022Review
- Hampering the early aggregation of PrP-E200K protein by charge-based inhibitors: a computational study.Journal of computer-aided molecular design · 2021Article
- Lipid Modulation in the Formation of β-Sheet Structures. Implications for De Novo Design of Human Islet Amyloid Polypeptide and the Impact on β-Cell Homeostasis.Biomolecules · 2020Article
- Amyloidogenicity and cytotoxicity of des-Lys-1 human amylin provides insight into amylin self-assembly and highlights the difficulties of defining amyloidogenicity.Protein engineering, design & selection : PEDS · 2019Article
- Modulation of Amyloidogenesis Controlled by the C-Terminal Domain of Islet Amyloid Polypeptide Shows New Functions on Hepatocyte Cholesterol Metabolism.Frontiers in endocrinology · 2018Article
- Peptide Conjugates of Benzene Carboxylic Acids as Agonists and Antagonists of Amylin Aggregation.Bioconjugate chemistry · 2017Article
- Electrostatic Repulsion Governs TDP-43 C-terminal Domain Aggregation.PLoS biology · 2016Article
- Islet Amyloid Polypeptide: Structure, Function, and Pathophysiology.Journal of diabetes research · 2016Review
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To test the hypothesis that electrostatic repulsion is an important force opposing amyloid fibril assembly, we designed peptides that substitute strings of positively or negatively charged residues into the sequence of the amyloidogenic hormone amylin, which contributes to type 2 diabetes pathology. Arg-1 and Arg-2 substitute four positively charged arginines for segments that in structural models of amylin fibrils form the end of strand β1 and the beginning of strand β2, respectively. Mem-T substitutes negatively charged aspartates for the peptide segment with the largest avidity for membranes. All three charge-loaded peptides fibrillize poorly on their own and inhibit fibril elongation of WT-amylin at physiological ionic strength. The inhibition of WT-amylin fibril elongation rates is salt-dependent indicating that the analogs act through electrostatic interactions. Arg-1 protects against WT-amylin cytotoxicity towards a MIN6 mouse model of pancreatic β-cells, and Arg-2 protects at higher concentrations, whereas Mem-T has no effect. The most effective variant, Arg-1, inhibits WT-amylin fibril elongation rates with an IC50 of ~1 µM and cytotoxicity with an IC50 of ~50 µM, comparable to other types of fibrillization inhibitors reported in the literature. Taken together, these results suggest that electrostatic interactions can be exploited to develop new types of inhibitors of amyloid fibrillization and toxicity.
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