An Activity-Based Fluorescent Probe for Imaging Fluctuations of Peroxynitrite (ONOO−) in the Alzheimer's Disease Brain
Abstract
Peroxynitrite (ONOO−) plays a critical role in Alzheimer's disease (AD). To reveal the ONOO− influx in AD brains, an activatable activity-based fluorescence probe Rd-DPA3 was designed by a structure-modulated strategy. Taking advantage of ONOO−-initiated two-step cascade reactions of a novel chemical trigger, Rd-DPA3 specifically responds to ONOO− in 0.3 mM of other reactive oxygen species (ROS) and varied proteins, and gives an intensive fluorescence enhancement (F/F0=50). Moreover, with its mitochondria-targeting ability, Rd-DPA3 can be used to efficiently monitor the alternations of intracellular ONOO− levels in cerebral cells during oxidative stress. Significantly, due to NIR emission and good blood-brain barrier (BBB) crossing ability, Rd-DPA3 is suitable for in vivo imaging of cerebral ONOO− influx and illustrating an age-dependent accumulation of ONOO− in AD mice brains.
- Publication:
-
Angewandte Chemie
- Pub Date:
- September 2022
- DOI:
- 10.1002/ange.202206894
- Bibcode:
- 2022AngCh.13406894W