ArticleBiochemistry2014
Rationally designed, nontoxic, nonamyloidogenic analogues of human islet amyloid polypeptide with improved solubility.
Article in Biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 42 citations in OpenAlex.
- Unveiling the multifaceted potential of amyloid fibrils: from pathogenic myths to biotechnological marvels.Biophysical reviews · 2024Review
- Analysis of Sheep and Goat IAPP Provides Insight into IAPP Amyloidogenicity and Cytotoxicity.Biochemistry · 2022Article
- Differential Effects of Aromatic Residues on Amyloid Formation and Cytotoxicity of Human IAPP.Biochemistry · 2022Article
- Tuning the rate of aggregation of hIAPP into amyloid using small-molecule modulators of assembly.Nature communications · 2022Article
- Contribution of the 12-17 hydrophobic region of islet amyloid polypeptide in self-assembly and cytotoxicity.Frontiers in molecular biosciences · 2022Article
- Ultra-Fast Insulin-Pramlintide Co-Formulation for Improved Glucose Management in Diabetic Rats.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Optimized experimental pre-treatment strategy for temporary inhibition of islet amyloid polypeptide aggregation.Biochemistry and biophysics reports · 2021Article
- Microcanonical insights into the physicochemical stability of the coformulation of insulin with amylin analogues.Journal of molecular modeling · 2021Article
- Cryo-EM structure of islet amyloid polypeptide fibrils reveals similarities with amyloid-β fibrils.Nature structural & molecular biology · 2020Article
- A co-formulation of supramolecularly stabilized insulin and pramlintide enhances mealtime glucagon suppression in diabetic pigs.Nature biomedical engineering · 2020Article
- Analysis of Baboon IAPP Provides Insight into Amyloidogenicity and Cytotoxicity of Human IAPP.Biophysical journal · 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
- Synergistic long-range effects of mutations underlie aggregation propensities of amylin analogues.Journal of molecular modeling · 2019Article
- Amyloidogenicity, Cytotoxicity, and Receptor Activity of Bovine Amylin: Implications for Xenobiotic Transplantation and the Design of Nontoxic Amylin Variants.ACS chemical biology · 2018Article
- The receptor for advanced glycation endproducts is a mediator of toxicity by IAPP and other proteotoxic aggregates: Establishing and exploiting common ground for novel amyloidosis therapies.Protein science : a publication of the Protein Society · 2018Review
- Evolutionary Adaptation and Amyloid Formation: Does the Reduced Amyloidogenicity and Cytotoxicity of Ursine Amylin Contribute to the Metabolic Adaption of Bears and Polar Bears?Israel journal of chemistry · 2017Article
- Pramlintide Antagonizes Beta Amyloid (Aβ)- and Human Amylin-Induced Depression of Hippocampal Long-Term Potentiation.Molecular neurobiology · 2017Article
- Cyclic AC253, a novel amylin receptor antagonist, improves cognitive deficits in a mouse model of Alzheimer's disease.Alzheimer's & dementia (New York, N. Y.) · 2017Article
- Amylin-mediated control of glycemia, energy balance, and cognition.Physiology & behavior · 2016Review
- Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Human islet amyloid polypeptide (hIAPP or amylin) is a polypeptide hormone produced in the pancreatic β-cells that plays a role in glycemic control. hIAPP is deficient in type 1 and type 2 diabetes and is a promising adjunct to insulin therapy. However, hIAPP rapidly forms amyloid, and its strong tendency to aggregate limits its usefulness. The process of hIAPP amyloid formation is toxic to cultured β-cells and islets, and islet amyloid formation in vivo has been linked to β-cell death and islet graft failure. An analogue of hIAPP with a weakened tendency to aggregate, denoted pramlintide (PM), has been approved for clinical applications, but suffers from poor solubility, particularly at physiological pH, and its unfavorable solubility profile prevents coformulation with insulin. We describe a strategy for rationally designing analogues of hIAPP with improved properties; key proline mutations are combined with substitutions that increase the net charge of the molecule. An H18R/G24P/I26P triple mutant and an H18R/A25P/S28P/S29P quadruple mutant are significantly more soluble at neutral pH than hIAPP or PM. They are nonamyloidogenic and are not toxic to rat INS β-cells. The approach is not limited to these examples; additional analogues can be designed using this strategy. To illustrate this point, we show that an S20R/G24P/I26P triple mutant and an H18R/I26P double mutant are nonamyloidogenic and significantly more soluble than human IAPP or PM. These analogues and second-generation derivatives are potential candidates for the coformulation of IAPP with insulin and other polypeptides.
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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.