Supramolecular Inhibition of Amyloid Fibrillation by Cucurbit[7]uril

Abstract

Amyloid fibrils are insoluble protein aggregates comprised of highly ordered b-sheet structures and they are involved in the pathology of amyloidoses, such as Alzheimers 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 b-amyloid by capturing phenylalanine (Phe) residues, which are crucial to the hydro- phobic 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.