An Activity‐Based Fluorescent Probe for Imaging Fluctuations of Peroxynitrite (ONOO−) in the Alzheimer's Disease Brain

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 ch...

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Published in:Angewandte Chemie International Edition 2022-09, Vol.61 (36), p.e202206894-n/a
Main Authors: Wang, Pengzhan, Yu, Le, Gong, Jiankang, Xiong, Jianhua, Zi, Soyu, Xie, Hua, Zhang, Fan, Mao, Zhiqiang, Liu, Zhihong, Kim, Jong Seung
Format: Article
Language:English
Subjects:
Activity-Based Sensing
Alternations
Alzheimer's Disease
Blood-brain barrier
Cascade chemical reactions
Chemical reactions
Fluorescence
Fluorescent indicators
Fluorescent Probe
In Vivo Imaging
Medical imaging
Mitochondria
Neurodegenerative diseases
Neuroimaging
Oxidative stress
Peroxynitrite
Reactive oxygen species
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Summary: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. Combining the ONOO−‐initiated cascade reactions of a novel chemical trigger and a new NIR emissive Rhodol fluorophore, an activity‐based NIR fluorescent probe for ONOO− in Alzheimer's disease (AD) brains was constructed. Real‐time imaging of ONOO− in AD mice and age‐dependent accumulation of ONOO− in AD mouse brains have been demonstrated with the probe.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202206894