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    • 6. 发明申请
    • SCREENING FOR INHIBITORS OF HCV AMPHIPATHIC HELIX (AH) FUNCTION
    • 筛选HCV双价体螺旋(AH)功能抑制剂
    • WO2010039195A3
    • 2010-05-27
    • PCT/US2009005306
    • 2009-09-23
    • UNIV LELAND STANFORD JUNIORGLENN JEFFREY SCHO NAM-JOONYANG WENJIN
    • GLENN JEFFREY SCHO NAM-JOONYANG WENJIN
    • G01N33/68G01N33/92
    • 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.
    • 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。 本发明的方法例如以高通量形式向脂质囊泡中添加AH肽; 该添加可以在不存在或存在候选药剂的情况下进行。 测量表观囊泡大小的变化,并与对照样品比较。 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药剂抑制。