利用固相合成技术获得抑制 DNA 修复核酸内切酶 SNM1A 的含胸腺嘧啶核苷类似物。
Deploying solid-phase synthesis to access thymine-containing nucleoside analogs that inhibit DNA repair nuclease SNM1A.
机构信息
Department of Biology and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
School of Chemistry and Trinity Biomedical Sciences Institute, Trinity College Dublin, 152-160 Pearse St., Dublin 2, Ireland.
出版信息
Org Biomol Chem. 2023 Jul 19;21(28):5873-5879. doi: 10.1039/d3ob00836c.
Abstract
Nucleoside analogs show useful bioactive properties. A versatile solid-phase synthesis that readily enables the diversification of thymine-containing nucleoside analogs is presented. The utility of the approach is demonstrated with the preparation of a library of compounds for analysis with SNM1A, a DNA damage repair enzyme that contributes to cytotoxicity. This exploration provided the most promising nucleoside-derived inhibitor of SNM1A to date with an IC of 12.3 μM.
摘要
核苷类似物具有有用的生物活性。本文提出了一种通用的固相合成方法，可轻松实现含胸腺嘧啶核苷类似物的多样化。该方法的实用性通过制备用于与 SNM1A 分析的化合物文库得到了证明，SNM1A 是一种导致细胞毒性的 DNA 损伤修复酶。该研究提供了迄今为止最有前途的 SNM1A 核苷衍生抑制剂，其 IC 为 12.3 μM。
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