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000909070 1001_ $$00000-0002-4301-3106$$aMaity, Debabrata$$b0$$eCorresponding author
000909070 245__ $$aCucurbit[7]uril Inhibits Islet Amyloid Polypeptide Aggregation by Targeting N Terminus Hot Segments and Attenuates Cytotoxicity.
000909070 260__ $$aWeinheim$$bWiley-VCH$$c2022
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000909070 520__ $$aTwo 'hot segments' within an islet amyloid polypeptide are responsible for its self-assembly, which in turn is linked to the decline of β-cells in type 2 diabetes (T2D). A readily available water-soluble, macrocyclic host, cucurbit[7]uril (CB[7]), effectively inhibits islet amyloid polypeptide (IAPP) aggregation through ion-dipole and hydrophobic interactions with different residues of the monomeric peptide in its random-coil conformation. A HSQC NMR study shows that CB[7] likely modulates IAPP self-assembly by interacting with and masking major residues present in the 'hot segments' at the N terminus. CB[7] also prevents the formation of toxic oligomers and inhibits seed-catalyzed fibril proliferation. Importantly, CB[7] recovers rat insulinoma cells (RIN-m) from IAPP-assembly associated cytotoxicity.
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000909070 650_7 $$2Other$$aamyloid fibrils
000909070 650_7 $$2Other$$acucurbit[7]uril
000909070 650_7 $$2Other$$aislet amyloid polypeptides
000909070 650_7 $$2Other$$amacrocyclic hosts
000909070 650_7 $$2Other$$aprotein assembly
000909070 650_7 $$2Other$$atype 2 diabetes
000909070 650_7 $$2NLM Chemicals$$aAmyloid
000909070 650_7 $$2NLM Chemicals$$aHeterocyclic Compounds, 2-Ring
000909070 650_7 $$2NLM Chemicals$$aImidazolidines
000909070 650_7 $$2NLM Chemicals$$aIslet Amyloid Polypeptide
000909070 650_7 $$2NLM Chemicals$$aMacrocyclic Compounds
000909070 650_7 $$2NLM Chemicals$$acucurbit(7)uril
000909070 650_2 $$2MeSH$$aAmyloid: chemistry
000909070 650_2 $$2MeSH$$aAnimals
000909070 650_2 $$2MeSH$$aDiabetes Mellitus, Type 2
000909070 650_2 $$2MeSH$$aHeterocyclic Compounds, 2-Ring
000909070 650_2 $$2MeSH$$aImidazolidines
000909070 650_2 $$2MeSH$$aInsulin-Secreting Cells
000909070 650_2 $$2MeSH$$aIslet Amyloid Polypeptide: chemistry
000909070 650_2 $$2MeSH$$aMacrocyclic Compounds
000909070 650_2 $$2MeSH$$aRats
000909070 7001_ $$0P:(DE-HGF)0$$aOh, Yujeong$$b1
000909070 7001_ $$0P:(DE-Juel1)145165$$aGremer, Lothar$$b2
000909070 7001_ $$0P:(DE-Juel1)166306$$aHoyer, Wolfgang$$b3$$eCorresponding author
000909070 7001_ $$00000-0003-3414-6617$$aMagzoub, Mazin$$b4
000909070 7001_ $$0P:(DE-HGF)0$$aHamilton, Andrew D$$b5$$eCorresponding author
000909070 773__ $$0PERI:(DE-600)1478547-X$$a10.1002/chem.202200456$$gVol. 28, no. 38$$n38$$pe202200456$$tChemistry - a European journal$$v28$$x0947-6539$$y2022
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