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COMPUTATIONALLY DESIGNED INHIBITORS OF AMYLOIDOSIS

机译:计算设计的淀粉样抑制剂

摘要

Embodiments of the present invention include methods and systems for designing inhibitors of amyloidosis in humans, domesticated animals, and wild animals as well as inhibitors of amyloidosis designed by the methods and systems. Methods and systems for designing inhibitors of amyloidosis are largely computational, in nature, and are directed to designing various types of polymers, small-molecule organic compounds, organometallic compounds, or non-chemical physical processes that can target the extended-a-strand and a-sheet regions of amyloidogenic protein and polypeptide intermediates in order to prevent aggregation of those intermediates into protofibrils and fibrils that, in turn, recruit additional native-conformation proteins and polypeptides into amyloidogenic intermediates and that additionally aggregate to form higher-order structures, such as plaques observed in the brains of patients suffering from the various spongiform encephalopathies.
机译:本发明的实施方案包括设计人,家养动物和野生动物中淀粉样变性抑制剂的方法和系统,以及通过该方法和系统设计的淀粉样变性抑制剂。设计淀粉样变性抑制剂的方法和系统本质上是大量计算的,旨在设计各种类型的聚合物,小分子有机化合物,有机金属化合物或可以靶向延伸的α-链的非化学物理过程。淀粉样蛋白形成的蛋白质和多肽中间体的a-折叠区域,以防止这些中间体聚集成原纤维和原纤维,而原纤维和原纤维又将其他天然构象的蛋白和多肽募集到淀粉样蛋白形成的中间体中,并另外聚集形成更高阶的结构,例如如在患有各种海绵状脑病的患者的大脑中观察到的斑块。

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