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

• Published in: Bioorganic & medicinal chemistry letters Vol. 26; no. 7; pp. 1784 - 1788
• Main Authors: Jung, Seung-Jin, Lee, Jun Young, Kim, Tae Ho, Lee, Dong-Eun, Jeon, Jongho, Yang, Seung Dae, Hur, Min Goo, Min, Jung-Joon, Park, Yong Dae
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.04.2016; Elsevier
• Subjects: Alzheimer Disease - diagnosis; Alzheimer Disease - pathology; Alzheimer’s disease (AD); Amyloid beta-Protein Precursor - analysis; Amyloid plaque; Animals; Boronic acid; Boronic Acids - chemistry; Boronic Acids - pharmacokinetics; Brain - pathology; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Fluorescent Dyes - chemistry; Fluorescent Dyes - pharmacokinetics; Fluorescent probe; Life Sciences & Biomedicine; Mice; Mice, Transgenic; Optical Imaging - methods; Pharmacology & Pharmacy; Physical Sciences; Plaque, Amyloid - diagnosis; Plaque, Amyloid - pathology; Protein Aggregation, Pathological - diagnosis; Protein Aggregation, Pathological - pathology; Science & Technology; Amyloid plaque; Boronic acid; Alzheimer’s disease (AD); Fluorescent probe; DESIGN; DEPOSITS; IMAGING AGENT; Alzheimer's disease (AD); DERIVATIVES; BRAIN
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2016.02.042

[Display omitted] 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, FAβ/F0) in fluorescence intensity as a response to Aβ aggregates, with a blue shift (105nm) in the maximum emission wavelength. We found that boronic acid as a functional group improved the binding affinity (KD value=0.79±0.05μM 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.