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    Methods and compositions for derepression of IAP-inhibited caspase
    4.
    发明授权
    Methods and compositions for derepression of IAP-inhibited caspase 失效
    用于抑制IAP抑制半胱天冬酶的方法和组合物

    公开(公告)号：US06911426B2

    公开(公告)日：2005-06-28

    申请号：US10302811

    申请日：2002-11-21

    申请人： John C. Reed ,  Richard A. Houghten ,  Adel Nefzi ,  John M. Ostresh ,  Clemencia Pinilla ,  Kate Welsh

    发明人： John C. Reed ,  Richard A. Houghten ,  Adel Nefzi ,  John M. Ostresh ,  Clemencia Pinilla ,  Kate Welsh

    IPC分类号： C12Q1/02 ,  A61K38/00 ,  A61P1/04 ,  A61P3/10 ,  A61P5/16 ,  A61P9/10 ,  A61P17/06 ,  A61P19/02 ,  A61P21/00 ,  A61P21/04 ,  A61P25/00 ,  A61P29/00 ,  A61P35/00 ,  A61P37/00 ,  A61P37/02 ,  A61P43/00 ,  C07K5/10 ,  C07K5/103 ,  C07K5/107 ,  C07K5/11 ,  C07K5/117 ,  C07K7/04 ,  C07K7/06 ,  C12Q1/37

    CPC分类号： C07K7/06 ,  A61K38/00 ,  C07K5/1008 ,  C07K5/1016 ,  C07K5/1019 ,  C07K5/1024 ,  C07K5/1027

    摘要： The invention provides isolated agents having a core peptide selected from the group consisting of Core peptides 5 through 39 and 42 through 55, wherein the agent derepresses an IAP-inhibited caspase. Also provided is an isolated agent having a core structure selected from any of the structures shown in FIGS. 5, 9, 10, 14B, and 21-24 wherein said agent derepresses an IAP-inhibited caspase. The invention further provides a method of derepressing an IAP-inhibited caspase. The method consists of contacting an IAP-inhibited caspase with an effective amount of an agent to derepress an IAP-inhibited caspase, the agent having a core motif selected from the group consisting of a core peptide having a sequence set forth in any of Core peptides 4 through 39 and 42 through 55, and a core structure selected from the group consisting of TPI759, TPI882, TPI914 or TPI927. The methods of the invention also can be used for promoting apoptosis in a cell and for reducing the severity of a pathology characterized by reduced levels of apoptosis. Methods for identifying agents that derepress an IAP-inhibited caspase are also provided.

    摘要翻译： 本发明提供了具有选自核心肽5至39和42至55的核心肽的分离的试剂，其中所述试剂减阻IAP抑制的半胱天冬酶。 还提供了一种隔离剂，其具有选自图1和图2所示的任何结构的芯结构。 5,9,10,14B和21-24，其中所述试剂去抑制IAP抑制的半胱天冬酶。 本发明还提供了一种去抑制IAP抑制的半胱天冬酶的方法。 该方法包括使IAP抑制的半胱天冬酶与有效量的试剂接触以对抑制IAP-抑制的半胱天冬酶进行脱保护，该试剂具有选自核心肽的核心基序，所述核心基序具有核心肽 4至39和42至55，以及选自TPI759，TPI882，TPI914或TPI927的核心结构。 本发明的方法还可用于促进细胞凋亡和降低以凋亡水平降低为特征的病理学的严重性。 还提供了用于鉴定抑制IAP抑制的半胱天冬酶的药剂的方法。