Department of Regulatory Bioorganic Chemistry, The Institute of Scientific and Industrial Research (SANKEN), Osaka University, 8-1 Mihogaoka, Ibaraki 567-0047, Japan.
Department of Regulatory Bioorganic Chemistry, The Institute of Scientific and Industrial Research (SANKEN), Osaka University, 8-1 Mihogaoka, Ibaraki 567-0047, Japan.
Bioorg Med Chem Lett. 2024 Dec 1;114:129985. doi: 10.1016/j.bmcl.2024.129985. Epub 2024 Oct 10.
Myotonic dystrophy type 1 (DM1) is caused by the aberrant expansion of CTG repeats within the DMPK gene. This study investigated the potential binding of "X-linker-Y" type molecules to the CTG/CTG motif present in CTG repeats, using heterocyclic units X and Y capable of forming complementary hydrogen bonds with nucleobases. Among the tested molecules, the heterodimer of 2-amino-1,8-naphthyridine (X) and 3-aminoisoquinoline (Y) showed significant binding to the CTG/CTG motif. NMR analysis suggested hydrogen-bonded interactions between 3-aminoisoquinoline and thymine.
肌强直性营养不良 1 型（DM1）是由 DMPK 基因内的 CTG 重复序列异常扩增引起的。本研究利用能够与碱基形成互补氢键的杂环单元 X 和 Y，研究了“X 连接子-Y”型分子与 CTG 重复序列中存在的 CTG/CTG 基序的潜在结合。在测试的分子中，2-氨基-1,8-萘啶（X）和 3-氨基异喹啉（Y）的杂二聚体与 CTG/CTG 基序表现出显著的结合。NMR 分析表明，3-氨基异喹啉与胸腺嘧啶之间存在氢键相互作用。
