This title appears in the Scientific Report :
2022
Please use the identifier:
http://dx.doi.org/10.1002/chem.202200456 in citations.
Cucurbit[7]uril Inhibits Islet Amyloid Polypeptide Aggregation by Targeting N Terminus Hot Segments and Attenuates Cytotoxicity.
Cucurbit[7]uril Inhibits Islet Amyloid Polypeptide Aggregation by Targeting N Terminus Hot Segments and Attenuates Cytotoxicity.
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 polypep...
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Personal Name(s): | Maity, Debabrata (Corresponding author) |
---|---|
Oh, Yujeong / Gremer, Lothar / Hoyer, Wolfgang (Corresponding author) / Magzoub, Mazin / Hamilton, Andrew D (Corresponding author) | |
Contributing Institute: |
Strukturbiochemie; IBI-7 |
Published in: | Chemistry - a European journal, 28 (2022) 38, S. e202200456 |
Imprint: |
Weinheim
Wiley-VCH
2022
|
DOI: |
10.1002/chem.202200456 |
PubMed ID: |
35532096 |
Document Type: |
Journal Article |
Research Program: |
Information Processing in Neuronal Networks |
Subject (ZB): | |
Publikationsportal JuSER |
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. |