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1. 发明申请

WO2013116903A1 METHODS FOR THE CHARACTERISATION OF INTERACTION SITES ON TARGET PROTEINS 审中-公开
标题翻译：表征目标蛋白质相互作用位点的方法
公开(公告)号：WO2013116903A1
公开(公告)日：2013-08-15
申请号：PCT/AU2013/000110
申请日：2013-02-07
申请人： PHYLOGICA LIMITED , CAMBRIDGE ENTERPRISE LIMITED
发明人： WATT, Paul , HARDWICK, Bryn , McKENZIE, Grahame , VENKITARAMAN, Ashok
IPC分类号： C07K14/195 , A61K38/16 , C12Q1/02
CPC分类号： G01N33/6845 , C07K14/195 , C12N15/1079 , C40B30/02 , G01N33/5041 , G01N33/6842 , G01N2500/10 , G06F19/16
摘要： The present invention relates to improved and integrated methods for the characterisation of an interaction site on a target protein that modulates the phenotype of a mammalian cell, such as a phenotype other than death and/or reduced growth. Such methods of the present invention include those to identify a target protein modulates such a phenotype of a mammalian cell, and optionally to characterise an interaction site on said target protein. Such identification and characterisation methods are useful in the development of research tools and/or therapeutics, such protein/peptide or small molecule therapeutics. Accordingly, the present invention also relates to methods of: identification of a ligand, such as a small molecule ligand, that binds to such a target protein; and identification a compound being a candidate modulator of said phenotype of a mammalian cell. The invention further relates to peptides or proteins, or fragments, variants and/or derivatives thereof) comprising certain amino acid sequences, nucleic acids encoding such peptides or proteins and uses of such peptides or proteins or of such nucleic acids.
摘要翻译：本发明涉及用于表征调节哺乳动物细胞的表型的靶蛋白上的相互作用位点的改进和综合方法，例如除死亡和/或减少的生长之外的表型。本发明的这些方法包括鉴定靶蛋白调节哺乳动物细胞的这种表型的方法，以及任选地表征所述靶蛋白上的相互作用位点。这种鉴定和表征方法可用于开发研究工具和/或治疗剂，例如蛋白质/肽或小分子治疗剂。因此，本发明还涉及以下方法：鉴定与这种靶蛋白结合的配体，如小分子配体; 以及鉴定作为所述哺乳动物细胞表型的候选调节剂的化合物。本发明还涉及包含某些氨基酸序列的肽或蛋白质或其片段，变体和/或衍生物，编码这些肽或蛋白质的核酸以及这种肽或蛋白质或这种核酸的用途。

2. 发明申请

WO2016075468A1 A METHOD OF SCREENING FOR MODULATION OF CELL SIGNALLING PATHWAYS 审中-公开
标题翻译：用于调制细胞信号通路的筛选方法
公开(公告)号：WO2016075468A1
公开(公告)日：2016-05-19
申请号：PCT/GB2015/053432
申请日：2015-11-12
申请人： CAMBRIDGE ENTERPRISE LIMITED
发明人： HARDWICK, Bryn , VENKITARAMAN, Ashok , EMERY, Amy , MCKENZIE, Grahame
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6897 , C12Q2563/107
摘要： A method for the identification of new therapeutic targets and protein interaction sites for use in drug discovery. In particular the invention relates to a method for identifying inhibitors of a cell signalling pathway, the method comprising (1) providing a population of mammalian cells, each mammalian cell having an active cell signalling pathway and comprising: (a) a first heterologous nucleic acid comprising; (i) a nucleotide sequence encoding a first detectable reporter and, (ii) a constitutive regulatory element which is operably linked to the nucleotide sequence; and, (b) a second heterologous nucleic acid comprising: (i) a first nucleotide sequence encoding a repressor molecule, for example an RNA or protein, which inactivates, inhibits or suppresses expression of the first detectable reporter, (ii) a second nucleotide sequence encoding a second detectable reporter; and (iii) a signal-activated regulatory element which is activated by said cell signalling pathway, said signal-activated regulatory element being operably linked to the first and second nucleotide sequences, (2) introducing a library of test compounds into said population of mammalian cells, and; (3) determining the expression of the first and the second detectable reporters in one or more of the population of transfected cells, wherein expression of the first detectable reporter but not the second detectable reporter in a transfected cell is indicative that the test biomolecule expressed by the nucleic acid in the cell inhibits said cell signalling pathway.
摘要翻译：用于鉴定用于药物发现的新的治疗靶标和蛋白质相互作用位点的方法。特别地，本发明涉及用于鉴定细胞信号传导途径抑制剂的方法，所述方法包括（1）提供哺乳动物细胞群，每个哺乳动物细胞具有活性细胞信号传导途径，并包含：（a）第一异源核酸包括; （i）编码第一可检测报告基因的核苷酸序列，和（ii）与核苷酸序列可操作地连接的组成型调控元件; 和（b）第二异源核酸，其包含：（i）编码阻抑物分子（例如RNA或蛋白质）的第一核苷酸序列，其失活，抑制或抑制第一可检测报告物的表达，（ii）第二核苷酸序列编码第二个可检测的报告物; 所述信号激活的调节元件可操作地连接到第一和第二核苷酸序列，（2）将测试化合物文库导入所述哺乳动物群体中细胞和（3）确定在一个或多个转染细胞群体中的第一和第二可检测报告基因的表达，其中在转染细胞中第一可检测报道基因而不是第二可检测报告基因的表达指示测试生物分子由细胞中的核酸抑制所述细胞信号传导途径。

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