Myotonic dystrophy type 1 (DM1) is an autosomal dominantly inherited degenerative disease with a slow progression. At the present, there is no commercially available treatment, but sustained effort is currently undertaken for the development of a promising lead compound. In the present paper we report the development of a fast, versatile, and cost-effective affinity capillary electrophoresis (ACE) method for the screening and identification of potential drug candidates targeting pathological ARN probes relevant for DM1. The affinity studies were conducted in physiologically relevant conditions using 50 mM HEPES buffer (pH 7.4) in a fused silica capillary dynamically coated with poly(ethylene oxide), by testing a library of potential ligands against (CUG)₅₀ RNA as target probe with a total run time of 4–5 h/ligand. For the most promising ligands, their affinity parameters were assessed and some results formerly reported on the affinity of pentamidine (PTMD) and neomycin against CUG repeats were confirmed. To the best of the authors’ knowledge, the estimated binding stoichiometry for some of the tested compounds (i.e., ~ 121:1 for PTMD against the tested RNA probe) is reported for the first time. Additionally, the potential of a novel pentamidine like compound, namely 1,2-ethane bis-1-amino-4-benzamidine (EBAB) with much lower in vivo toxicity than its parent compound has also been confirmed studying its effect on a live cell model by fluorescence microscopy. Further tests, such as the evaluation of the rescue in the mis-splicing of the involved genes, can be performed to corroborate the potential therapeutic value of EBAB in DM1 treatment.

中文翻译：

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亲和毛细管电泳鉴定1型肌强直性营养不良中的活性药物

1型强直性肌营养不良症（DM1）是一种常染色体显性遗传性退行性疾病，进展缓慢。目前，尚无可商购的治疗方法，但目前正在进行持续的努力以开发有前途的前导化合物。在本文中，我们报告了一种快速，通用且具有成本效益的亲和毛细管电泳（ACE）方法的开发，该方法用于筛选和鉴定针对与DM1相关的病理性ARN探针的潜在候选药物。通过测试针对（CUG）₅₀的潜在配体库，在生理相关条件下使用50 mM HEPES缓冲液（pH 7.4）在动态涂有聚（环氧乙烷）的熔融石英毛细管中进行亲和力研究。RNA作为靶探针，总运行时间为4–5 h /配体。对于最有前途的配体，评估了它们的亲和力参数，并证实了以前报道的喷他idine（PTMD）和新霉素对CUG重复序列的亲和力的一些结果。据作者所知，首次报道了某些被测化合物的结合化学计量（即PTMD相对于被测RNA探针约为121：1）。此外，研究其对活细胞的作用也已证实，其体内毒性比其母体化合物低得多的新型戊烷类化合物（即1,2-乙烷双-1-氨基-4-苯甲m（EBAB））的潜力荧光显微镜观察模型。进一步的测试，例如评估所涉及基因错接时的拯救，