高等学校化学学报

高等学校化学学报

• 研究论文 • 上一篇    

DNA中的5-氟-2'-脱氧尿苷(FdU)修饰增强cGAS介导的免疫反应

马竟科1, 管文丽1, 周永昌1, 余智磊1, 航 海1, 张瀚文1, 任梦田2,3, 周传政1   

  1. 1. 元素有机化学全国重点实验室，有机新物质创造前沿科学中心，南开大学化学学院化学生物学系

    2. 天津工业大学化学学院 3. 天津工业大学沧州研究院

  • 收稿日期:2026-05-28 修回日期:2026-06-18 出版日期:2026-06-21 发布日期:2026-06-21
  • 通讯作者: 周传政
  • 基金资助:
    国家重点研发计划(批准号：2025YFA0920900)、国家自然科学基金(批准号：92581104，22377059，22407100)、天津市自然科学基金(批准号：25ZXWCSY00100)和河北省自然科学基金(批准号：B2025110005)资助

Incorporation of 5-Fluoro-2'-Deoxyuridine (FdU) into DNA Enhances cGAS-Mediated Immune Responses

MA Jingke1, GUAN Wenli1, ZHOU Yongchang1, Yu Zhilei1, HANG Hai1, ZHANG Hanwen1, REN Mengtian2,3*, ZHOU Chuanzheng1*   

  1. 1. State Key Laboratory of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, Department of Chemical Biology, College of Chemistry, Nankai University 2. School of Chemistry, Tiangong University 3. Cangzhou Institute of Tiangong University,
  • Received:2026-05-28 Revised:2026-06-18 Online:2026-06-21 Published:2026-06-21
  • Supported by:
    Supported by the National Key Research and Development Program of China (No. 2025YFA0920900), the National Natural Science Foundation of China (Nos. 92581104, 22377059 and 22407100), the Natural Science Foundation of Tianjin (No. 25ZXWCSY00100) and the Hebei Natural Science Foundation (No. B2025110005)

PDF (PC)

补充材料

1

摘要： 通过合成5-氟-2′-脱氧尿苷(FdU)定点修饰的双链DNA，系统研究了FdU修饰对双链DNA激活先天免疫受体cGAS的调节作用. 研究结果表明，FdU修饰的双链DNA对cGAS表现出更高的结合亲和力，并在体外显著增强了cGAS合成2′，3′-cGAMP的能力. 在小鼠和人源免疫细胞中，FdU 修饰的双链DNA通过激活cGAS通路诱导了更强的I型干扰素表达和促炎免疫反应，且增强水平与双链DNA中FdU的修饰数量呈正相关. 这些发现揭示了氟代嘧啶类化疗药物与抗肿瘤免疫之间潜在的关联，并表明FdU修饰的双链DNA是有潜力的cGAS激动剂，在免疫治疗领域具有应用前景.

关键词: DNA修饰, 氟代尿苷, 免疫治疗

Abstract: In this study, we synthesized 5-fluoro-2′-deoxyuridine (FdU)-modified dsDNA and systematically evaluated how FdU modification affects its ability to activate the innate immune receptor cyclic GMP–AMP synthase (cGAS). FdU-modified dsDNA exhibited increased binding affinity for cGAS and enhanced cGAS-dependent 2′,3′-cGAMP production in vitro. In both murine and human immune cells, FdU-modified dsDNA elicited stronger type I interferon and pro-inflammatory responses through activation of the cGAS, with response magnitude positively correlating with the number of FdU substitutions. These findings establish a potential immunological link between fluoropyrimidine chemotherapy and antitumor immunity, and highlight FdU modification as a promising strategy for engineering potent cGAS agonists for immunotherapeutic applications.

Key words: DNA modification, Fluoropyrimidine; Immunotherapy

中图分类号: 

TrendMD: