TY  - JOUR
AU  - Maity, Debabrata
AU  - Oh, Yujeong
AU  - Gremer, Lothar
AU  - Hoyer, Wolfgang
AU  - Magzoub, Mazin
AU  - Hamilton, Andrew D
TI  - Cucurbit[7]uril Inhibits Islet Amyloid Polypeptide Aggregation by Targeting N Terminus Hot Segments and Attenuates Cytotoxicity.
JO  - Chemistry - a European journal
VL  - 28
IS  - 38
SN  - 0947-6539
CY  - Weinheim
PB  - Wiley-VCH
M1  - FZJ-2022-02988
SP  - e202200456
PY  - 2022
N1  - Kein Post-print vorhanden
AB  - 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.
KW  - Amyloid: chemistry
KW  - Animals
KW  - Diabetes Mellitus, Type 2
KW  - Heterocyclic Compounds, 2-Ring
KW  - Imidazolidines
KW  - Insulin-Secreting Cells
KW  - Islet Amyloid Polypeptide: chemistry
KW  - Macrocyclic Compounds
KW  - Rats
KW  - amyloid fibrils (Other)
KW  - cucurbit[7]uril (Other)
KW  - islet amyloid polypeptides (Other)
KW  - macrocyclic hosts (Other)
KW  - protein assembly (Other)
KW  - type 2 diabetes (Other)
KW  - Amyloid (NLM Chemicals)
KW  - Heterocyclic Compounds, 2-Ring (NLM Chemicals)
KW  - Imidazolidines (NLM Chemicals)
KW  - Islet Amyloid Polypeptide (NLM Chemicals)
KW  - Macrocyclic Compounds (NLM Chemicals)
KW  - cucurbit(7)uril (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:35532096
UR  - <Go to ISI:>//WOS:000803082700001
DO  - DOI:10.1002/chem.202200456
UR  - https://juser.fz-juelich.de/record/909070
ER  -