Inhibition of Aggregation of Amyloid β42 by Arginine-Containing Small Compounds
Inhibition of Aggregation of Amyloid β42 by Arginine-Containing Small Compounds
复制标题
DOI：
10.1271/bbb.110879
复制
发表时间：
2012-04-01
影响因子：
1.6
通讯作者：
Kamijo, Shunsuke
中科院分区：
文献类型：
--
作者：
Kawasaki, Takayasu;Kamijo, Shunsuke
在许多情况下，蛋白质的聚集与阿尔茨海默病（AD）等神经退行性疾病有关。能够抑制蛋白质聚集的小化合物预计不仅可用于治疗疾病，还可用于探测聚集蛋白质的结构。在之前使用噬菌体展示的研究中，我们发现由四个或七个氨基酸组成的富含精氨酸的短肽与可溶性42残基淀粉样蛋白β（Aβ42）结合并抑制球聚体（37/48 kDa寡聚体）的形成。在本研究中，我们使用 SciFinder 搜索服务搜索含精氨酸的小分子，并通过十二烷基硫酸钠 (SDS)-PAGE 和硫黄素 T 结合测定测试其对 A beta 42 聚集的抑制活性。人们发现市售的Arg-Arg-7-氨基-4-三氟甲基香豆素对Aβ42的球聚体和原纤维的形成表现出显着的抑制活性。这种嵌合型三肽有望作为Aβ聚集过程的有效抑制剂的种子分子。
Aggregations of proteins are in many cases associated with neurodegenerative diseases such as Alzheimer's (AD). Small compounds capable of inhibiting protein aggregation are expected to be useful for not only in the treatment of disease but also in probing the structures of aggregated proteins. In previous studies using phage display, we found that arginine-rich short peptides consisting of four or seven amino acids bound to soluble 42-residue amyloid beta (A beta 42) and inhibited globulomer (37/48 kDa oligomer) formation. In the present study, we searched for arginine-containing small molecules using the SciFinder searching service and tested their inhibitory activities against A beta 42 aggregation, by sodium dodecyl sulfate (SDS)-PAGE and thioflavine T binding assay. Commercially available Arg-Arg-7-amino-4-trifluoromethylcoumarin was found to exhibit remarkable inhibitory activities to the formation of the globulomer and the fibril of A beta 42. This chimera-type tri-peptide is expected to serve as the seed molecule of a potent inhibitor of the A beta aggregation process.