Cucurbit[7]uril Inhibits Islet Amyloid Polypeptide Aggregation by Targeting N Terminus Hot Segments and Attenuates Cytotoxicity.
Chemistry
; 28(38): e202200456, 2022 Jul 06.
Article
em En
| MEDLINE
| ID: mdl-35532096
ABSTRACT
Two "hot segments" within an islet amyloid polypeptide are responsible for its self-assembly, which in turn is linked to the decline of ß-cells in typeâ
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 Nâ
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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Diabetes Mellitus Tipo 2
/
Células Secretoras de Insulina
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article