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    • 1. 发明授权
    • Modulating robo: ligand interactions
    • 调节robo:配体相互作用
    • US06270984B1
    • 2001-08-07
    • US09540245
    • 2000-03-31
    • Corey S. GoodmanThomas KiddKatja BroseMarc Tessier-Lavigne
    • Corey S. GoodmanThomas KiddKatja BroseMarc Tessier-Lavigne
    • G01N3383
    • C07K14/70503A61K38/00C07K14/4702G01N33/566G01N33/68G01N2333/43573G01N2500/02
    • Disclosed are methods and compositions for identifying agents which modulate the interaction of Robo and a Robo ligand and for modulating the interaction of Robo and a Robo ligand. The methods for identifying Robo:ligand modulators find particular application in commercial drug screens. These methods generally comprise (1) combining a Robo polypeptide, a Slit polypeptide and a candidate agent under conditions whereby, but for the presence of the agent, the Robo and Slit polypeptides engage in a first interaction, and (2) determining a second interaction of the Robo and Slit polypeptides in the presence of the agent, wherein a difference between the first and second interactions indicates that the agent modulates the interaction of the Robo and Slit polypeptides. The subject methods of modulating the interaction of Robo and a Robo ligand involve combining a Robo polypeptide, a Slit polypeptide and a modulator under conditions whereby, but for the presence of the modulator, the Robo and Slit polypeptides engage in a first interaction, whereby the Robo and Slit polypeptides engage in a second interaction different from the first interaction. In a particular embodiment, the modulator is dominant negative form of the Robo or Slit polypeptide.
    • 公开了用于鉴定调节Robo和Robo配体的相互作用并调节Robo和Robo配体的相互作用的试剂的方法和组合物。 用于鉴定Robo:配体调节剂的方法在商业药物筛选中发现具体应用。 这些方法通常包括(1)在条件下组合Robo多肽,狭缝多肽和候选试剂,但是对于所述试剂的存在,所述Robo和狭缝多肽参与第一相互作用,和(2)确定第二相互作用 的Robo和Slit多肽,其中所述第一和第二相互作用之间的差异指示所述试剂调节所述Robo和Slit多肽的相互作用。 调节Robo和Robo配体的相互作用的主题方法包括在条件下组合Robo多肽,狭缝多肽和调节剂,但是对于调节剂的存在,Robo和Slit多肽参与第一相互作用,由此 Robo和Slit多肽参与与第一相互作用不同的第二相互作用。 在一个具体实施方案中,调节剂是Robo或Slit多肽的显性阴性形式。