Premium
Development of aggregation inhibitors for amyloid‐ β peptides and their evaluation by quartz‐crystal microbalance
Author(s) -
Okuno Hiroaki,
Mori Kanae,
Okada Tomoko,
Yokoyama Yuusaku,
Suzuki Hideharu
Publication year - 2007
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2007.00509.x
Subject(s) - quartz crystal microbalance , chemistry , derivative (finance) , amyloid (mycology) , bioassay , biophysics , organic chemistry , inorganic chemistry , biology , adsorption , financial economics , economics , genetics
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 A β 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 mm 2 electrode. Furthermore, bioassay results showed no toxicity of the inhibitor itself against IMR‐32 neuroblastoma cells, and remarkably reduced cytotoxicities of both A β 1–40 and A β 1–42 were exhibited in the presence of these inhibitors. The KLVFF‐(EEX)3 derivative was the most efficient A β aggregation among the inhibitors examined here.