%0 Journal Article
%A Maity, Debabrata
%A Oh, Yujeong
%A Gremer, Lothar
%A Hoyer, Wolfgang
%A Magzoub, Mazin
%A Hamilton, Andrew D
%T Cucurbit[7]uril Inhibits Islet Amyloid Polypeptide Aggregation by Targeting N Terminus Hot Segments and Attenuates Cytotoxicity.
%J Chemistry - a European journal
%V 28
%N 38
%@ 0947-6539
%C Weinheim
%I Wiley-VCH
%M FZJ-2022-02988
%P e202200456
%D 2022
%Z Kein Post-print vorhanden
%X 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.
%K Amyloid: chemistry
%K Animals
%K Diabetes Mellitus, Type 2
%K Heterocyclic Compounds, 2-Ring
%K Imidazolidines
%K Insulin-Secreting Cells
%K Islet Amyloid Polypeptide: chemistry
%K Macrocyclic Compounds
%K Rats
%K amyloid fibrils (Other)
%K cucurbit[7]uril (Other)
%K islet amyloid polypeptides (Other)
%K macrocyclic hosts (Other)
%K protein assembly (Other)
%K type 2 diabetes (Other)
%K Amyloid (NLM Chemicals)
%K Heterocyclic Compounds, 2-Ring (NLM Chemicals)
%K Imidazolidines (NLM Chemicals)
%K Islet Amyloid Polypeptide (NLM Chemicals)
%K Macrocyclic Compounds (NLM Chemicals)
%K cucurbit(7)uril (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:35532096
%U <Go to ISI:>//WOS:000803082700001
%R 10.1002/chem.202200456
%U https://juser.fz-juelich.de/record/909070