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. Supramolecular strategy: Amyloid fibrillation of insulin and β‐amyloid was modulated by using cucurbit[7]uril (CB[7]). CB[7] exhibits high binding affinity for phenylalanine residues, which are crucial to the hydrophobic interactions formed during amyloid fibrillation. This supramolecular strategy based on a residue‐specific interaction has potential for the development of a therapeutic agent for amyloidosis.