Journal Article

FZJ-2022-02988

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Cucurbit[7]uril Inhibits Islet Amyloid Polypeptide Aggregation by Targeting N Terminus Hot Segments and Attenuates Cytotoxicity.

Maity, D. (Corresponding author) ; Oh, Y. ; Gremer, L.FZJ* ; Hoyer, W. (Corresponding author)FZJ* ; Magzoub, M. ; Hamilton, A. D. (Corresponding author)

2022
Wiley-VCH Weinheim

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Please use a persistent id in citations: doi:10.1002/chem.202200456

Abstract: 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.

Keyword(s): Amyloid: chemistry (MeSH) ; Animals (MeSH) ; Diabetes Mellitus, Type 2 (MeSH) ; Heterocyclic Compounds, 2-Ring (MeSH) ; Imidazolidines (MeSH) ; Insulin-Secreting Cells (MeSH) ; Islet Amyloid Polypeptide: chemistry (MeSH) ; Macrocyclic Compounds (MeSH) ; Rats (MeSH) ; amyloid fibrils ; cucurbit[7]uril ; islet amyloid polypeptides ; macrocyclic hosts ; protein assembly ; type 2 diabetes ; Amyloid ; Heterocyclic Compounds, 2-Ring ; Imidazolidines ; Islet Amyloid Polypeptide ; Macrocyclic Compounds ; cucurbit(7)uril

Note: Kein Post-print vorhanden

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Contributing Institute(s):

1. Strukturbiochemie (IBI-7)

Research Program(s):

1. 5244 - Information Processing in Neuronal Networks (POF4-524) (POF4-524)

Appears in the scientific report 2022

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Database coverage:
; Chemical Reactions ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; Index Chemicus ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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