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    • 5. 发明申请
    • SCREENING FOR INHIBITORS OF HCV AMPHIPATHIC HELIX (AH) FUNCTION
    • 筛选HCV雄性HELIX(AH)功能的抑制剂
    • WO2010039195A2
    • 2010-04-08
    • PCT/US2009/005306
    • 2009-09-23
    • THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITYGLENN, Jeffrey S.CHO, Nam-JoonYANG, Wenjin
    • GLENN, Jeffrey S.CHO, Nam-JoonYANG, Wenjin
    • C12Q1/70
    • C07K14/005C12N2770/24222
    • Screening methods are provided for identifying pharmacologic inhibitors of HCV amphipathic helix (AH) function, which inhibitors are useful in the prevention and treatment of HCV infection. Also provided are compounds useful in the inhibition of viral replication. The methods of the invention are based on the unexpected discovery that the presence of an AH, e.g. an AH of an HCV polypeptide, causes an increase in the apparent diameter of the vesicles. The methods of the invention provide for addition of AH peptides to lipid vesicles, for example in a high-throughput format; which addition may be performed in the absence or presence of a candidate pharmacologic agent. The change in apparent vesicle size is measured, and compared to control samples. An increase in vesicle size or aggregation is indicative of AH function being present; and a lack of increase is indicative that the AH function is absent or has been inhibited by a test agent.
    • 提供筛选方法用于鉴定HCV两亲性螺旋(AH)功能的药理学抑制剂,该抑制剂可用于预防和治疗HCV感染。 还提供了可用于抑制病毒复制的化合物。 本发明的方法基于意想不到的发现,即AH的存在,例如, HCV多肽的AH引起囊泡表观直径的增加。 本发明的方法提供了将AH肽添加到脂质囊泡中,例如以高通量形式加入; 该添加可以在不存在或存在候选药理剂的情况下进行。 测量明显囊泡大小的变化,并与对照样品进行比较。 囊泡大小或聚集的增加表明存在AH功能; 并且缺乏增加表明AH功能不存在或已被测试者抑制。