期刊
ANALYTICAL CHEMISTRY
卷 94, 期 44, 页码 15261-15269出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.2c02532
关键词
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资金
- National Natural Science Foundation of China [22022601, U1967221, 91632116]
- Science Innovation 2030-Brain Science and Brain-Inspired Intelligence Technology Major Projects [2021ZD0201103, 2021ZD0201803]
By rational design, a series of D-pi-A-based trisubstituted alkenes were developed, which showed high binding affinities to alpha-syn fibrils and promising potential for the in vitro neuropathological staining of Lewy pathologies.
Lewy pathologies, which mainly consist of insoluble alpha-synuclein (alpha-syn) aggregates, are the hallmarks of Parkinson's disease and many other neurodegenerative diseases termed synucleinopathies. Detection of Lewy pathologies with optical methods is of interest for preclinical studies, while the alpha-syn fluorescent probe is still in great demand. By rational design, we obtained a series of D-pi-A-based trisubstituted alkenes with acceptable optical properties and high binding affinities to alpha-syn fibrils. Among these probes, FPQXN and TQXN-2 exhibited high binding affinities (6 and 8 nM, respectively), significant fluorescence enhancements (17.2-and 26.6-fold, respectively), and satisfying quantum yields (36.5% and 10.4%, respectively), which met the need for the in vitro neuropathological staining of Lewy pathologies in the PD brain sections. In addition, TQXN-2 showed great potential in fluorescent discrimination of Lewy pathologies and A beta plaques. Our research provides flexible tools for in vitro detection of alpha-syn aggregates and offers new structural frameworks for the further development of alpha-syn fluorescent probes.
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