Cucurbit[7]uril Inhibits Islet Amyloid Polypeptide Aggregation by Targeting N Terminus Hot Segments and Attenuates Cytotoxicity
| Autor: | Debabrata Maity, Yujeong Oh, Lothar Gremer, Wolfgang Hoyer, Mazin Magzoub, Andrew D. Hamilton |
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| Rok vydání: | 2022 |
| Předmět: |
Bridged-Ring Compounds
Amyloid Macrocyclic Compounds pharmacology [Bridged-Ring Compounds] pharmacology [Imidazoles] Organic Chemistry Imidazoles General Chemistry cucurbit(7)uril Imidazolidines Heterocyclic Compounds 2-Ring Catalysis Islet Amyloid Polypeptide Rats Diabetes Mellitus Type 2 Insulin-Secreting Cells ddc:540 Animals Humans |
| Zdroj: | Chemistry-a European journal 28(38), na/na (2022). doi:10.1002/chem.202201698 |
| ISSN: | 1521-3765 0947-6539 |
| DOI: | 10.1002/chem.202200456 |
| Popis: | Two "hot segments" within an islet amyloid polypeptide are responsible for its self-assembly, which in turn is linked to the decline of β-cells in type 2 diabetes (T2D). A readily available water-soluble, macrocyclic host, cucurbit[7]uril (CB[7]), effectively inhibits islet amyloid polypeptide (IAPP) aggregation through ion-dipole and hydrophobic interactions with different residues of the monomeric peptide in its random-coil conformation. A HSQC NMR study shows that CB[7] likely modulates IAPP self-assembly by interacting with and masking major residues present in the "hot segments" at the N terminus. CB[7] also prevents the formation of toxic oligomers and inhibits seed-catalyzed fibril proliferation. Importantly, CB[7] recovers rat insulinoma cells (RIN-m) from IAPP-assembly associated cytotoxicity. |
| Databáze: | OpenAIRE |
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