Development of aggregation inhibitors for amyloid-β peptides and their evaluation by quartz-crystal microbalance
Development of aggregation inhibitors for amyloid-β peptides and their evaluation by quartz-crystal microbalance
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DOI：
10.1111/j.1747-0285.2007.00509.x
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发表时间：
2007-05-01
影响因子：
3
通讯作者：
Suzuki, Hideharu
中科院分区：
文献类型：
--
作者：
Okuno, Hiroaki;Mori, Kanae;Suzuki, Hideharu
合成了一系列由分子识别元件(KLVFF)和基于氨基酸类似物的聚集破坏部分(具有静电和亲水性)组成的淀粉样β聚集抑制剂。应用石英晶体微天平(QCM)方法成功地评价了Aβ聚集的抑制活性，这种抑制活性随频率的增加而观察到。在4.9 mm(2)的电极上，QCM可以检测到具有频率差异的质量变化，对应于每增加30pg质量就减少1赫兹频率。此外，生物测定结果表明，该抑制剂本身对IMR-32神经母细胞瘤细胞没有毒性，Aβ1-40和Aβ1-42的细胞毒性在这些抑制剂的存在下都显著降低。KLVFF-(EEX)3衍生物是所考察的抑制剂中最有效的Aβ聚集。
A series of amyloid-beta 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 beta 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 beta 1-40 and A beta 1-42 were exhibited in the presence of these inhibitors. The KLVFF-(EEX)3 derivative was the most efficient A beta aggregation among the inhibitors examined here.