Small-molecule aggregates inhibit amyloid polymerization
Small-molecule aggregates inhibit amyloid polymerization
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DOI：
10.1038/nchembio.65
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发表时间：
2008-03-01
影响因子：
14.8
通讯作者：
Shoichet, Brian K.
中科院分区：
文献类型：
--
作者：
Feng, Brian Y.;Toyama, Brandon H.;Shoichet, Brian K.
许多淀粉样蛋白抑制剂类似于形成化学聚集体的分子，已知它们可以抑制许多蛋白质。八种已知的化学聚集剂以胶体抑制的特征方式抑制酵母和小鼠朊病毒蛋白Sup35和recMoPrP的淀粉样蛋白形成。类似地，三种已知的抗淀粉样蛋白分子以去垢剂依赖性方式抑制β-内酰胺酶，这表明它们也形成胶体聚集体。在电子显微照片中，胶体定位于预成型纤维并阻止新纤维的形成。他们还阻断了 Sup35 朊病毒对酵母细胞的感染，这表明胶体抑制可能与更多的生物环境有关。
Many amyloid inhibitors resemble molecules that form chemical aggregates, which are known to inhibit many proteins. Eight known chemical aggregators inhibited amyloid formation of the yeast and mouse prion proteins Sup35 and recMoPrP in a manner characteristic of colloidal inhibition. Similarly, three known anti-amyloid molecules inhibited P-lactamase in a detergent-dependent manner, which suggests that they too form colloidal aggregates. The colloids localized to preformed fibers and prevented new fiber formation in electron micrographs. They also blocked infection of yeast cells with Sup35 prions, which suggests that colloidal inhibition may be relevant in more biological milieus.