霍克斯特修饰通过菌株促进的亚酸循环添加来运输功能分子进入细胞核
Hiroki Makanai1, Daisuke Mochizuki1, Tatsuya Nishihara1
1Department of Chemistry and Biological Science, College of Science and Engineering, Aoyama Gakuin University, 5-10-1 Fuchinobe, Chuo-ku, Sagamihara 252-5258, Japan.
Bioorganic & medicinal chemistry letters
|August 8, 2024
概括
研究人员使用点击化学修改了霍克斯特核染料,以创建光探针. 这些探头跟踪线粒体功能,可用于核成像和医疗治疗.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 细胞生物学 细胞生物学
背景情况:
- 将功能分子输送到细胞核对于理解核功能和开发医疗治疗至关重要.
- 霍克斯特分子是一个成熟的核染色剂.
- 点击化学反应,如应变促进的亚酸环添加 (SPAAC),为分子修饰提供了高效的方法.
研究的目的:
- 用SPAAC反应来修改霍希斯特分子,以创建新的功能探针.
- 描述修改后的 Hoechst 衍生品的特性.
- 研究这些衍生物在核和线粒体中的双定位以及监测线粒体功能的潜力.
主要方法:
- 制备Hoechst衍生物与亚基 (Hoe-N3) 的制备.
- 在Hoe-N3和含有二基环氧化物 (DBCO) 的分子 (胺,TAMRA,Cy5) 之间SPAAC反应的表征.
- 评估改性Hoechst衍生物的DNA结合特性.
- 在活细胞中评估细胞吸收和局部化,包括对线粒体去极化反应.
主要成果:
- 通过SPAAC反应成功合成了何氏衍生物 (何氏胺,何氏,何氏5).
- 修改后的霍克斯特衍生品保留了它们的DNA结合能力.
- 霍特-TAMRA和霍特-Cy5在细胞核和线粒体中都显示出双重积累.
- 这些探针最初积聚在线粒体中,并在线粒体脱极化后转移到核中.
结论:
- 修改后的Hoechst分子可以作为有效的光探针用于双核和线粒体成像.
- 在脱极化后,探针从线粒体转移到核,可以监测线粒体功能.
- 这些新型探测器有可能用于核功能可视化和医疗治疗.
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