药理学
点击化学
炎症
生物化学
药物输送
细胞生物学
生物物理学
纳米载体
作者
Zhi Du,Chun Liu,Hualong Song,Peter Scott,Zhenqi Liu,Jinsong Ren,Xiaogang Qu
出处
期刊:Chem
[Elsevier]
日期:2020-08-06
卷期号:6 (8): 2060-2072
被引量:22
标识
DOI:10.1016/j.chempr.2020.06.002
摘要
Summary Targeted bioorthogonal catalysis holds great potential for localized prodrug activation. Although enantiomerically pure drugs are of vital importance in the clinic, chiral drug synthesis by bioorthogonal reactions in living systems is scarcely reported. Toward this goal, we constructed chirally modified Pd catalysts for the asymmetric transfer hydrogenation (ATH) reaction by using sodium formate as the biocompatible reductant. By combining the ATH reaction and chemotaxis of neutrophil membrane, we achieved inflammation site-selective chiral drug synthesis in living cells. As a proof of concept, we synthesized the chiral model drug ibuprofen in situ by a targeted ATH reaction to alleviate inflammation in the mouse paw as an in vivo model. Compared with controls, the neutrophil-membrane-coated chiral Pd catalysts exhibited inflammation-targeted capability and enantioselectivity simultaneously in the anti-inflammatory action. This study could offer a novel perspective for bioorthogonal catalysis in targeted prodrug activation.
科研通智能强力驱动
Strongly Powered by AbleSci AI