An activatable small-molecule fluorogenic probe for detection and quantification of beta-amyloid aggregates

Extracellular accumulation of beta amyloid (A beta) peptides in the brain is thought to be a pathological hallmark and initial event before the symptom starts of Alzheimer's patients. Herein, we developed two series of benzo[d] thiazole-based small-molecule compounds (BM1-BM4, BPM1-BPM4) with a donor-acceptor (D-A) or donor pi-acceptor (D-pi-A) architecture, respectively, based on structure-activity relationship. Among them, the optimized BPM1 not only displayed the highest binding affinity to A beta aggregates over other proteins or A beta monomers, but was readily activated its fluorescence with 10-fold fluorescence enhancement, allowing for specifically and sensitively detecting A beta aggregates. BPM1 also exhibits several other advantages including low molecular weight, low cytotoxicity and excellent biological stability. Besides, cell staining results confirmed that SK-N-BE (2) cells can be fluorescently lighted up as well as cell permeability and damage when treated with BPM1-bound A beta(1-42) aggregates.