Highly Sensitive Near-Infrared Fluorophores for in Vivo Detection of Amyloid‑β Plaques in Alzheimer’s Disease
Alzheimer’s disease (AD) is pathologically characterized by the accumulation of β-amyloid (Aβ) deposits in the parenchymal and cortical brain. In this work, we designed, synthesized, and evaluated a series of near-infrared (NIR) probes with electron donor–acceptor end groups interacting through a π-...
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Veröffentlicht in: | Journal of medicinal chemistry 2015-09, Vol.58 (17), p.6972-6983 |
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Sprache: | eng |
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Zusammenfassung: | Alzheimer’s disease (AD) is pathologically characterized by the accumulation of β-amyloid (Aβ) deposits in the parenchymal and cortical brain. In this work, we designed, synthesized, and evaluated a series of near-infrared (NIR) probes with electron donor–acceptor end groups interacting through a π-conjugated system for the detection of Aβ deposits in the brain. Among these probes, 3b and 3c had excellent fluorescent properties (emission maxima > 650 nm and high quantum yields) and displayed high sensitivity and high affinities to Aβ aggregates (3b, K d = 8.8 nM; 3c, K d = 1.9 nM). Both 3b and 3c could readily penetrate the blood–brain barrier with high initial brain uptake and fast to moderate washout from the brain. In vivo NIR imaging revealed that 3b and 3c could efficiently differentiate transgenic and wild-type mice. In summary, our research provides new hints for developing smarter and more activatable NIR probes targeting Aβ. |
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ISSN: | 0022-2623 1520-4804 |
DOI: | 10.1021/acs.jmedchem.5b00861 |