Development of aggregation inhibitors for amyloid-β peptides and their evaluation by quartz-crystal microbalance

A series of amyloid‐β aggregation inhibitors composed of a molecular recognition element (KLVFF) and an aggregation‐disrupting part (having an electrostatic and hydrophilic nature) based on amino acid analogs have been synthesized. A quartz‐crystal microbalance (QCM) method was applied and found to be very successful in evaluating the inhibitory activity of the Aβ aggregation, which was observed when the frequency was increased. The QCM can detect a mass change with differences in frequency that correspond to a 1 Hz frequency decrease per 30 pg mass increase on a 4.9 mm2 electrode. Furthermore, bioassay results showed no toxicity of the inhibitor itself against IMR‐32 neuroblastoma cells, and remarkably reduced cytotoxicities of both Aβ1–40 and Aβ1–42 were exhibited in the presence of these inhibitors. The KLVFF‐(EEX)3 derivative was the most efficient Aβ aggregation among the inhibitors examined here.