{"title":"Studies on in vitro modulatory effects to base excision repair enzymes induced by small molecule binding to Deaminated CAG repeat hairpin","authors":"Anisa Ulhusna , Asako Murata , Kazuhiko Nakatani","doi":"10.1016/j.bmcl.2025.130152","DOIUrl":null,"url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"120 ","pages":"Article 130152"},"PeriodicalIF":2.2000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic & Medicinal Chemistry Letters","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0960894X25000617","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/19 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
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.
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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