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

[Display omitted] •A new molecule, iQN, the heterodimer of 2-amino-1,8-naphthyridine and 3-aminoisoquinoline, has been prepared.•iQN binds to the CTG/CTG triad found in the CTG repeats.•NMR analysis revealed that iQN recognizes the CTG/CTG triad through hydrogen bonding and induces nucleobase flip-o...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2024-12, Vol.114, p.129985, Article 129985
Main Authors: Sakurabayashi, Shuhei, Yamada, Takeshi, Nakatani, Kazuhiko
Format: Article
Language:English
Subjects:
CTG repeat
Mismatched base pair
Nuclear Magnetic Resonance (NMR)
Small molecule ligand
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Summary:[Display omitted] •A new molecule, iQN, the heterodimer of 2-amino-1,8-naphthyridine and 3-aminoisoquinoline, has been prepared.•iQN binds to the CTG/CTG triad found in the CTG repeats.•NMR analysis revealed that iQN recognizes the CTG/CTG triad through hydrogen bonding and induces nucleobase flip-out. 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.
ISSN:0960-894X
1464-3405
1464-3405
DOI:10.1016/j.bmcl.2024.129985