皮兰/皮龙:用于亚细胞硫化的输送和标签的"点击释放"捐赠者
Wei Huang1, Nipuni Gunawardhana1, Yunlei Zhang1
1Department of Chemistry, Stony Brook University, 100 Nicolls Road, Stony Brook, NY 11790, United States.
Chemistry (Weinheim an der Bergstrasse, Germany)
|November 20, 2023
概括
研究人员开发了新型的pyranthiones,通过点击反应有效释放硫化 (H2S). 这些化合物提供可调节的动力学,用于有针对性的输送,解决H2S供体开发的挑战,用于细胞信号传输.
科学领域:
- 化学生物学 化学生物学
- 药用化学 医学化学
- 生物化学 生化学
背景情况:
- 硫化 (H2S) 是一种关键的气传递物,参与各种疾病信号通路.
- 开发高效和可控制的H2S供体用于亚细胞输送仍然是一个重大挑战.
- 现有的方法往往缺乏可调节的释放动力学或高效率,用于精确的生物应用.
研究的目的:
- 设计和合成具有可调节释放动力学和高效率的新型H2S捐赠体.
- 为了探索一种新的点击和释放反应,用于控制的气传递器输送.
- 调查这些捐赠者的潜力,以准亚细胞和线粒体.
主要方法:
- 开发了一种使用pyrone/pyranthiones和bicyclononyne (BCN) 的点击释放反应.
- 研究了反应动力学,比较了pyranthiones和pyrones,并评估了biorthogonality.
- 在实验室和活细胞中合成了替代皮兰西,并评估了它们的H2S释放效率.
主要成果:
- 皮龙/皮兰西和 BCN 反应释放 CO2/COS,具有有效的二次速率常数.
- 皮兰西的反应速度比皮龙的反应速度更快,表现出更高的性能.
- 合成的皮兰西提供可调节的H2S释放动力学和高的体外释放效率,使线粒体向成为可能.
结论:
- 使用pyranthiones的新点击和释放策略为开发H2S捐赠者提供了一个有希望的平台.
- 这些pyranthiones表现出可调节的释放动力学和高效率,适合各种细胞动态.
- 开发的化合物显示出有针对性的H2S和COS传递的潜力,特别是在线粒体.
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