The heterodimer of 2-amino-1,8-naphthyridine and 3-aminoisoquinoline binds to the CTG/CTG triad via hydrogen bonding

IF 2.5 4区 医学 Q3 CHEMISTRY, MEDICINAL Bioorganic & Medicinal Chemistry Letters Pub Date : 2024-10-10 DOI:10.1016/j.bmcl.2024.129985
Shuhei Sakurabayashi, Takeshi Yamada, Kazuhiko Nakatani
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Abstract

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.

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2-氨基-1,8-萘啶和 3-氨基异喹啉的异二聚体通过氢键与 CTG/CTG 三元组结合。
肌营养不良症 1 型(DM1)是由 DMPK 基因中 CTG 重复序列的异常扩展引起的。本研究利用能与核碱基形成互补氢键的杂环单元 X 和 Y,研究了 "X-连接剂-Y "型分子与 CTG 重复序列中的 CTG/CTG 主题的潜在结合。在测试的分子中,2-氨基-1,8-萘啶(X)和 3-氨基异喹啉(Y)的杂二聚体显示出与 CTG/CTG 主题的显著结合。核磁共振分析表明,3-氨基异喹啉与胸腺嘧啶之间存在氢键相互作用。
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来源期刊
CiteScore
5.70
自引率
3.70%
发文量
463
审稿时长
27 days
期刊介绍: Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.
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