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2. 发明申请

US20070026463A1 Compositions and methods of mutant Nogo-66 domain proteins 审中-公开
标题翻译：突变Nogo-66结构域蛋白的组成和方法
公开(公告)号：US20070026463A1
公开(公告)日：2007-02-01
申请号：US11495061
申请日：2006-07-28
申请人： Yuhong Xie , Brian Bates , Janet Paulsen
发明人： Yuhong Xie , Brian Bates , Janet Paulsen
IPC分类号： C40B30/06 , G01N33/53 , C07H21/04 , C12P21/06 , C07K14/705
CPC分类号： G01N33/566 , C07K14/47 , C07K2319/61 , G01N2333/475 , G01N2500/02
摘要： To facilitate the study of Nogo-66 interaction with its neuronal receptors, and to explore therapeutic opportunities, the present invention provides mutant human Nogo-66 domain-based proteins that do not aggregate during isolation or purification procedures, and methods for using these proteins. Aggregates of Nogo-66 domain containing proteins do not effectively or efficiently bind to the NgR1 receptor, and therefore limit the utility of Nogo-66 domain-based reagents. To overcome aggregation problems, the invention provides proteins that comprise a mutant human Nogo-66 domain, wherein the cysteine at position 47 of the wild-type human Nogo-66 domain is mutated. The invention also provides for various Nogo-66 domain fusion reporter proteins that are able to bind to NgR1, and therefore can be used in high-throughput assays to identify drug candidate compounds that can block binding of the Nogo-66 domain to NgR1, indicating that these compounds may be potential therapeutic agents for neurodegenerative diseases and neuronal repair.
摘要翻译：为了促进Nogo-66与其神经元受体的相互作用的研究，并且为了探索治疗机会，本发明提供了在分离或纯化过程中不聚合的突变型人Nogo-66结构域的蛋白质，以及使用这些蛋白质的方法。含有Nogo-66结构域的蛋白质的聚集体不能有效或有效地结合NgR1受体，因此限制了Nogo-66结构域的试剂的效用。为了克服聚集问题，本发明提供了包含突变人Nogo-66结构域的蛋白质，其中野生型人Nogo-66结构域的位置47处的半胱氨酸被突变。本发明还提供了能够结合NgR1的各种Nogo-66结构域融合报道蛋白，因此可用于高通量测定以鉴定可阻断Nogo-66结构域与NgR1结合的药物候选化合物，表明这些化合物可能是神经变性疾病和神经元修复的潜在治疗剂。

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