Discovery of boronic acid-based fluorescent probes targeting amyloid-beta plaques in Alzheimer’s disease

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• 作者：Seung-Jin Jung^a ; Jun Young Lee^a ; Tae Ho Kim^c ; Dong-Eun Lee^a ; Jongho Jeon^a ; ^d ; Seung Dae Yang^a ; Min Goo Hur^a ; Jung-Joon Min^b ; Yong Dae Park^a ; ^b ; ^{ydpark@kaeri.re.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Alzheimer&rsquo ; s disease (AD) ; Amyloid plaque ; Boronic acid ; Fluorescent probe
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 April 2016
• 年：2016
• 卷：26
• 期：7
• 页码：1784-1788
• 全文大小：1211 K

文摘

A boronic acid-based fluorescent probe was developed for diagnosis of amyloid-β (Aβ) plaques from Alzheimer’s disease (AD). Probe 4c, which included boronic acid as a functional group, exhibited a significant increase (64.37-fold, F_Aβ/F₀) in fluorescence intensity as a response to Aβ aggregates, with a blue shift (105 nm) in the maximum emission wavelength. We found that boronic acid as a functional group improved the binding affinity (K_D value = 0.79 ± 0.05 μM for 4c) for Aβ aggregates and confirmed that 4c selectively stained Aβ plaques in brain sections from APP/PS1 mice. Ex vivo fluorescence imaging using mice (normal and APP/PS1) also revealed that 4c was able to penetrate the blood–brain barrier (BBB) and to stain Aβ plaques in the brain. From these results, we believe that 4c will be useful as a fluorescent probe in preclinical research related to AD. Furthermore, we believe that our results with boronic acid also provide valuable information for the development of a probe for Aβ plaques.