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    Oligomers that bind to ku protein
    6.
    发明授权
    Oligomers that bind to ku protein 失效
    结合ku蛋白的低聚物

    公开(公告)号：US06441158B1

    公开(公告)日：2002-08-27

    申请号：US09223139

    申请日：1998-12-30

    申请人： William S. Dynan ,  Sunghan Yoo

    发明人： William S. Dynan ,  Sunghan Yoo

    IPC分类号： C07H2104

    CPC分类号： C12N15/1137 ,  A61K38/00 ,  C12N2310/18 ,  C12N2310/53

    摘要： Disclosed are oligomers that bind Ku protein. These oligomers are useful for inhibiting activation of DNA-PK, treating certain forms of autoimmune disease, detection and purification of Ku protein, and identification of proteins that interact with Ku protein. Preferably, the oligomers are composed of nucleotides, nucleotide analogs, or a combination. Most preferably, the oligomers are composed of ribonucleotides. Also disclosed is a method of inhibiting DNA repair, a method of identifying cellular proteins that interact with Ku protein, and a method of treating autoimmune disease in patients with anti-Ku antibodies. The disclosed oligomers can have several preferred features, either alone or in combination, in addition to Ku binding. One such feature, referred to herein as inhibition activity, is inhibition of DNA-PK kinase activity. Another preferred feature, referred to herein as aptamer motifs, is the presence of one or more of the base sequences GCUUUCCCANNNAC, A(A/C)AUGA, and AACUUCGA. These sequences—referred to herein as aptamer motif 1, aptamer motif 2, and aptamer motif 3, respectively—are associated with Ku binding capability. Another preferred feature, referred to herein as aptamer structure, is the presence of a structure similar to the structure shown in FIG. 6A. This structure has the general formula 5′-A-B-C-D-C′-E-A′-3′, where A, B, C, D, C′, E, and A′ are components of the oligomer. In this structure, A and A′ interact to form a stem structure, C and C′ interact to form a stem structure, B and E make up a bulge region, and D is either a bulge or a loop. FIG. 6A depicts component D as a loop. Each of these preferred features (inhibition activity, aptamer motif, and aptamer structure) can be used either alone or in combination with one or both of the other characteristics.

    摘要翻译： 公开了结合Ku蛋白的寡聚体。 这些寡聚体可用于抑制DNA-PK的活化，治疗某些形式的自身免疫疾病，Ku蛋白的检测和纯化，以及与Ku蛋白相互作用的蛋白质的鉴定。 优选地，寡核苷酸由核苷酸，核苷酸类似物或组合组成。 最优选地，寡聚体由核糖核苷酸组成。 还公开了抑制DNA修复的方法，鉴定与Ku蛋白相互作用的细胞蛋白质的方法以及在抗Ku抗体患者中治疗自身免疫疾病的方法。 除了Ku结合之外，所公开的低聚物可以具有单独或组合的几个优选特征。 这里称为抑制活性的一个这样的特征是抑制DNA-PK激酶活性。 碱基序列GCUUUCCCANNNAC，A（A / C）AUGA和AACUUCGA中存在一个或多个碱基序列的另一优选特征。 这些序列 - 分别称为适体基序1，适体基序2和适体基序3 - 与Ku结合能力相关。 在本文中称为适体结构的另一个优选特征是存在类似于图1所示结构的结构。 6A。 该结构具有通式5'-A-B-C-D-C'-E-A'-3'，其中A，B，C，D，C'，E和A'是低聚物的组分。 在这种结构中，A和A'相互作用以形成茎结构，C和C'相互作用形成茎结构，B和E组成一个凸起区域，D是一个凸起或一个环。 图。 图6A将部件D描绘为循环。 这些优选特征（抑制活性，适体基序和适体结构）中的每一个可以单独使用或与一种或两种其它特征组合使用。