Chang Chung-ke, Jhan Cyong-Ru, Hou Ming-Hon
Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung 40227, Taiwan.
Curr Top Med Chem. 2015;15(14):1398-408. doi: 10.2174/1568026615666150413155030.
Expansion of trinucleotide repeats (TNRs) within genes plays a major role in pathology of various neurological diseases. The correlations of these unusual repetitive sequences with the aetiology of these diseases and the mechanism by which those repeats are expanded during replication have been extensively studied. Small-molecule ligands that bind to TNRs could provide potent biological applications. First, the length of the TNR is the most important determinant of these neurological diseases. Ligands that reduce the repeat length or impair repeat expansion may be used to delay onset and reduce the severity of these diseases. Interestingly, many important anticancer ligands and antibiotics have desirable qualities when interacting with TNR DNA, and may form the basis for the development of novel therapeutics against neurological diseases. Second, designed ligands that bind to expanded TNRs with high specificity based on the structural and chemical characteristics of these repeats can serve as diagnostic tools for determining repeat length and may have applications in preventive medicine. In this article we will review our current understanding of the interaction between DNA-binding ligands and TNRs.
基因内三核苷酸重复序列（TNRs）的扩增在多种神经疾病的病理过程中起主要作用。这些异常重复序列与这些疾病病因的相关性以及这些重复序列在复制过程中扩增的机制已得到广泛研究。与TNRs结合的小分子配体可提供强大的生物学应用。首先，TNR的长度是这些神经疾病的最重要决定因素。能够缩短重复长度或抑制重复序列扩增的配体可用于延缓疾病发作并减轻疾病严重程度。有趣的是，许多重要的抗癌配体和抗生素在与TNR DNA相互作用时具有理想的特性，可能成为开发新型神经疾病治疗药物的基础。其次，基于这些重复序列的结构和化学特征设计的能与扩增的TNRs高特异性结合的配体，可作为确定重复长度的诊断工具，并可能应用于预防医学。在本文中，我们将综述目前对DNA结合配体与TNRs相互作用的理解。
