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    Methods for identifying small molecules that modulate premature translation termination and nonsense mediated mRNA decay
    1.
    发明授权
    Methods for identifying small molecules that modulate premature translation termination and nonsense mediated mRNA decay 有权
    用于鉴定调节过早翻译终止和无义介导的mRNA衰变的小分子的方法

    公开(公告)号：US07927791B2

    公开(公告)日：2011-04-19

    申请号：US10521775

    申请日：2003-07-24

    申请人： Ellen M. Welch ,  Neil Gregory Almstead ,  Robert F. Rando ,  Mathew C. Pellegrini

    发明人： Ellen M. Welch ,  Neil Gregory Almstead ,  Robert F. Rando ,  Mathew C. Pellegrini

    IPC分类号： C12Q1/68 ,  C07H21/02

    CPC分类号： B82Y30/00 ,  G01N33/5308 ,  G01N2500/04

    摘要： The present invention relates to a method for screening and identifying compounds that modulate premature translation termination and/or nonsense-mediated messenger ribonucleic acid (“mRNA”) by interacting with a preselected target ribonucleic acid (“RNA”). In particular, the present invention relates to identifying compounds that bind to regions of the 28S ribosomal RNA (“rRNA”) and analogs thereof. Direct, noncompetitive binding assays are advantageously used to screen libraries of compounds for those that selectively bind to a preselected target RNA. Binding of target RNA molecules to a particular compound is detected using any physical method that measures the altered physical property of the target RNA bound to a compound. The structure of the compound attached to the labeled RNA is also determined. The methods used will depend, in part, on the nature of the library screened. The methods of the present invention provide a simple, sensitive assay for high-throughput screening of libraries of compounds to identify pharmaceutical leads.

    摘要翻译： 本发明涉及通过与预选的靶核糖核酸（“RNA”）相互作用来筛选和鉴定调节过早翻译终止和/或无义介导的信使核糖核酸（“mRNA”）的化合物的方法。 特别地，本发明涉及鉴定结合28S核糖体RNA（“rRNA”）的区域的化合物及其类似物。 直接的非竞争性结合测定法有利地用于筛选选择性结合预选靶RNA的化合物文库。 使用测量与化合物结合的靶RNA的改变的物理性质的任何物理方法检测靶RNA分子与特定化合物的结合。 还测定了附着于标记的RNA的化合物的结构。 所使用的方法部分取决于所筛选图书馆的性质。 本发明的方法提供了用于识别药物引线的化合物文库的高通量筛选的简单，灵敏的测定。