Sulfobutylether-β-Cyclodextrin for Inhibition and Rupture of Amyloid Fibrils

Anomalous aggregation of proteins into amyloid fibrils leads to various amyloidosis diseases including neurodegenerative disorders. Inhibition of fibrillation process and rupture of mature amyloid fibril/plaques using small organic molecules are the promising remedial strategies to combat neurodegenerative diseases. In this study, we present sulfobutylether-beta-cyclodextrin (SBE7 beta-CD), a water-soluble macrocycle, as an efficient additive to inhibit the fibril formation and also for the breakage of mature fibrils into nontoxic small particles. The steady-state and time-resolved fluorescence, circular dichroism measurements and fluorescence microscopic images collectively confirm the inhibition and rupture of the amyloid fibrils in the presence of SBE7 beta-CD. In one hand, the macrocyclic encapsulation of certain amino acid residues on the protein stabilizes the native form of insulin and lysozyme and prevents their transformation into the beta-sheet conformers, resulting in the inhibition of fibrillation. On the other hand, the degeneration of the fibril strands became feasible due to the overall positive charge of the fibril surface and the negative portals of the SBE7 beta-CD host. Positively, the nontoxic SBE7 beta-CD additive mitigates the toxicity of the system and is highly promising as therapeutics for amyloidosis.