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

Extracellular accumulation of β amyloid (Aβ) 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-π-acceptor (D-π-A) architecture, respectively, based on structure-activity relationship. Among them, the optimized BPM1 not only displayed the highest binding affinity to Aβ aggregates over other proteins or Aβ monomers, but was readily activated its fluorescence with 10-fold fluorescence enhancement, allowing for specifically and sensitively detecting Aβ 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 Aβ_1-42 aggregates.