Total degradation of extracellular amyloids by miniature artificial proteases

Abstract

A miniaturized mimic of the active site of a protease, chymotrypsin, was linked to a target recognition unit to generate “Miniature Artificial Proteases” (mAPs). Time-resolved MALDI-TOF data analyses indicated that mAPs cleaved every amide bond between Lys₁₆–Phe₂₀ of the amyloid β fragment (Aβ_12–21) and Aβ_1–40, resulting in inhibition of fibrillization and disruption of the preformed amyloid. Such a platform may offer not only new therapeutic options against various amyloidoses but also novel routes for the selective knockdown of specific proteins.