Studies on in vitro modulatory effects to base excision repair enzymes induced by small molecule binding to Deaminated CAG repeat hairpin

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Bioorganic & Medicinal Chemistry Letters Pub Date : 2025-02-19 DOI:10.1016/j.bmcl.2025.130152

Anisa Ulhusna , Asako Murata , Kazuhiko Nakatani

引用次数: 0

Abstract

Base Excision Repair (BER) pathway is correlated with nucleotide repeat instability. In this report, we investigated the modulatory effects of a DNA-binding small molecule, naphthyridine azaquinolone (NA), towards BER in an in vitro system. Thermal melting analyses demonstrated binding of NA to deaminated 5’-CAG-3′/5’-CAG-3′ triads in DNA. Furthermore, binding of NA to the deaminated CAG repeat hairpin was found to partially inhibit UNG2- and APE1-catalyzed reaction, suggesting a potential mechanism for NA-induced CAG repeat contraction via BER pathway.

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研究小分子与脱氨基 CAG 重复发夹结合对碱基切除修复酶的体外调节作用。

碱基切除修复（BER）途径与核苷酸重复不稳定性相关。在本报告中，我们研究了dna结合小分子萘嘧啶氮杂喹诺酮（NA）在体外系统中对BER的调节作用。热熔分析表明NA与DNA中脱去的5'-CAG-3'/5‘-CAG-3’三联体结合。此外，NA与脱氨CAG重复发夹的结合被发现部分抑制UNG2-和ape1催化的反应，这表明NA通过BER途径诱导CAG重复收缩的潜在机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioorganic & Medicinal Chemistry Letters 医学-医药化学

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.