A novel α-ketoamide reactivity-based two-photon fluorogenic probe for visualizing peroxynitrite in Parkinson’s disease models

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Abstract
Peroxynitrite (ONOO[ ] contributes to oxidative stress and neurodegeneration in Parkinson’s disease (PD). Developing a peroxynitrite probe would enable in situ visualization of the overwhelming ONOO− flux and understanding of the ONOO− stress-induced neuropathology of PD. Herein, a novel [ ]-ketoamide-based fluorogenic probe ( DFlu) was designed for ONOO− monitoring in multiple PD models. The results demonstrated that DFlu exhibits a fluorescence turn-on response to ONOO− with high specificity and sensitivity. The efficacy of DFlu for intracellular ONOO− imaging was demonstrated systematically. The results showed that DFlu can successfully visualize endogenous and exogenous ONOO− in cells derived from chemical and biochemical routes. More importantly, the two-photon excitation ability of DFlu has been well demonstrated by monitoring exogenous/endogenous ONOO− production and scavenging in live zebrafish PD models. This work provides a reliable and promising [ ]-ketoamide-based optical tool for identifying variations of ONOO− in PD models.
Funding Information
  • The National Natural Science Foundation of China (22077101)
  • The Open Project Program of Wuhan National Laboratory for Optoelectronics (2020WNLOKF023)
  • Natural Science Foundation of Shaanxi Province (2022JM-130)
  • the Joint Research Funds of Department of Science & Technology of Shaanxi Province and Northwestern Polytechnical University (2020GXLH-Z-008, 2020GXLH-Z-021, 2020GXLH-Z-023)
  • the China Postdoctoral Science Foundation (2022M711595, 2022M722595)
  • Postdoctoral Research Funding Schemes of Jiangsu Province (2021K036A)
  • the Natural Science Foundation of Ningbo (202003N4049, 202003N4065)

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