化探针的通用光关闭/启动策略:硬质排斥诱导的扭曲分子内电荷转移 (sr-TICT)
Kenjiro Hanaoka1, Takayuki Ikeno2, Shimpei Iwaki2
1Graduate School of Pharmaceutical Sciences, Keio University, 1-5-30 Shibakoen, Minoto-ku, Tokyo 105-8512, Japan.
Science advances
|February 16, 2024
概括
研究人员开发了一种新的光控制策略,称为硬体排斥诱导的TICT (sr-TICT),用于设计化探针. 这种方法通过分子内扭曲加速光灭,使生物事件可视化.
科学领域:
- 化学生物学 化学生物学
- 生物物理化学 生物物理化学
- 分子成像学分子成像学
背景情况:
- 化探针是通过光变化可视化生物过程的重要工具.
- 在探头中控制光调制通常依赖于各种策略.
- 罗达胺染料是开发光传感器的广泛使用的支架.
研究的目的:
- 用时间依赖密度函数理论 (TD-DFT) 来计算分析罗达胺染料中扭曲的分子内电荷转移 (TICT) 过程.
- 设计和合成基于罗达胺的新型化探针,利用一种新的光控制策略.
- 开发一种用于可视化细胞染色体P450 3A4 (CYP3A4) 的N-脱化活性的探针.
主要方法:
- 时间依赖密度函数理论 (TD-DFT) 在罗达胺染料中对TICT的计算分析.
- 新型罗达胺衍生物的设计和合成.
- 开发一种固体排斥诱导的TICT (sr-TICT) 光灭策略.
- 应用sr-TICT探针 (2-Me PeER) 进行基于CYP3A4活动的光激活细胞分类 (FACS).
主要成果:
- 计算分析阐明了罗达胺染料中的TICT机制.
- 建立了一个新的sr-TICT策略,通过分子内扭曲显著加速光火.
- 为检测CYP3A4的N-脱化活性,开发了一种特殊的探针2-Me PeER.
- 2-Me PeER 探测器在人类诱导的多能干细胞 (hiPSC) 衍生肝细胞和肠道细胞中成功实现了基于 CYP3A4 活动的 FACS.
结论:
- sr-TICT战略提供了一种通用和有效的方法,用于控制探头设计中的光.
- 开发的探针和方法方便在相关细胞模型中研究酶活性.
- 这种方法为推进生物事件可视化和药物代谢研究提供了强大的工具.
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