| 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.
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