MODULARLY ASSEMBLED SMALL MOLECULES FOR THE TREATMENT OF MYOTONIC DYSTROPHY TYPE 1
申请人:THE SCRIPPS RESEARCH INSTITUTE
公开号:US20160206753A1
公开(公告)日:2016-07-21
To study RNA function using small molecules, we designed bioactive, modularly assembled small molecules that target the noncoding expanded RNA repeat that causes myotonic dystrophy type 1 (Dm1), r(CUG)exp. Different modular assembly scaffolds were investigated including polyamines, alpha-peptides, beta-peptides, and peptide tertiary amides (PT As). Based on activity as assessed by improvement of DM1-associated defects, stability against proteases, cellular permeability, and toxicity, we discovered that constrained backbones, namely PT As, are optimal.
为了研究利用小分子化合物的RNA功能,我们设计了具有生物活性和模块化组装的小分子化合物,针对导致肌萎缩性侧索硬化症类型1(Dm1)的非编码扩展RNA重复序列r(CUG)exp。我们研究了不同的模块组装支架,包括多胺、α-肽、β-肽和肽三级酰胺(PTAs)。根据改善DM1相关缺陷的活性、对蛋白酶的稳定性、细胞渗透性和毒性的评估,我们发现约束的骨架,即PTAs,是最佳的选择。