Chapter title |
Development of Peptide-Based Inhibitors of Amylin Aggregation Employing Aromatic and Electrostatic Repulsion
|
---|---|
Chapter number | 2 |
Book title |
Rational Drug Design
|
Published in |
Methods in molecular biology, January 2018
|
DOI | 10.1007/978-1-4939-8630-9_2 |
Pubmed ID | |
Book ISBNs |
978-1-4939-8629-3, 978-1-4939-8630-9
|
Authors |
Adam A. Profit, Ruel Z. B. Desamero, Profit, Adam A., Desamero, Ruel Z. B. |
Abstract |
Human islet amyloid polypeptide (hIAPP) is a 37-residue hormone that is co-stored and co-secreted with insulin. In type 2 diabetes, the polypeptide misfolds to form amyloid plaques in the pancreas. The self-assembly of hIAPP has been linked to the loss of insulin production and β-cell death. Recent investigations have revealed that soluble oligomers of hIAPP are the cytotoxic species responsible for β-cell death and not insoluble amyloid fibrils. Compounds that prevent the self-assembly of hIAPP or drive self-assembly to the state of innocuous insoluble amyloid may be of potential therapeutic value. In this report we summarize key methods employed in our efforts to identify peptide-based modulators of amylin self-assembly that utilize π-electronic effects or electrostatic charge repulsion. These peptide-based modulators may serve as lead compounds for the development of more drug-like molecules and demonstrate that tuning π-electron density and employing charged amyloid disrupting elements are viable approaches toward the design of potential amyloid inhibitors. |
Mendeley readers
Geographical breakdown
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Unknown | 7 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Bachelor | 2 | 29% |
Student > Ph. D. Student | 1 | 14% |
Researcher | 1 | 14% |
Student > Master | 1 | 14% |
Unknown | 2 | 29% |
Readers by discipline | Count | As % |
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Physics and Astronomy | 1 | 14% |
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Materials Science | 1 | 14% |
Other | 0 | 0% |
Unknown | 2 | 29% |