Supramolecular inhibition of amyloid fibrillation by cucurbit[7]uril.
Amyloid fibrils are insoluble protein aggregates comprised of highly ordered β-sheet structures and they are involved in the pathology of amyloidoses, such as Alzheimer's disease. A supramolecular strategy is presented for inhibiting amyloid fibrillation by using cucurbit[7]uril (CB[7]). CB[7] prevents the fibrillation of insulin and β-amyloid by capturing phenylalanine (Phe) residues, which are crucial to the hydrophobic interactions formed during amyloid fibrillation. These results suggest that the Phe-specific binding of CB[7] can modulate the intermolecular interaction of amyloid proteins and prevent the transition from monomeric to multimeric states. CB[7] thus has potential for the development of a therapeutic strategy for amyloidosis.
Department of Chemistry, Pohang University of Science and Technology, Pohang, 790-784 (Republic of Korea).
Hong Hee
HH
Lee
Tae Su
TS
Choi
Shin Jung C
SJ
Lee
Jong Wha
JW
Lee
Junghong
J
Park
Young Ho
YH
Ko
Won Jong
WJ
Kim
Kimoon
K
Kim
Hugh I
HI
Kim
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry; D001952:Bridged-Ring Compounds / Q000737:chemistry*; D045744:Cell Line, Tumor; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D008969:Molecular Sequence Data; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils
D016229:Amyloid beta-Peptides; D001952:Bridged-Ring Compounds; D007093:Imidazoles; C456276:cucurbit(7)uril; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils
aggregation; cucurbit[7]uril; insulin; supramolecular chemistry; β-amyloid