한빛사논문
- 조회620
Jusung Ana,1, Peter Verwilstb,1, Hira Azizc,d,1, Jinwoo Shina,1, Sungsu Limc, Ilwha Kima, Yun Kyung Kimc,d,*, Jong Seung Kima,*
aDepartment of Chemistry, Korea University, Seoul, 02841, South Korea
bKU Leuven, Rega Institute for Medical Research, Medicinal Chemistry, 3000, Leuven, Belgium
cConvergence Research Center for Diagnosis, Treatment and Care System of Dementia, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, 02792, South Korea
dDivision of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology (UST), Seoul, 02792, South Korea
1These authors contributed equally to this work.
*Corresponding author.
Abstract
The pathological origin of Alzheimer's disease (AD) is still shrouded in mystery, despite intensive worldwide research efforts. The selective visualization of β-amyloid (Aβ), the most abundant proteinaceous deposit in AD, is pivotal to reveal AD pathology. To date, several small-molecule fluorophores for Aβ species have been developed, with increasing binding affinities. In the current work, two organic small-molecule dioxaborine-derived fluorophores were rationally designed through tailoring the hydrophobicity with the aim to enhance the binding affinity for Aβ1-42 fibrils —while concurrently preventing poor aqueous solubility—via biannulate donor motifs in D-π-A dyes. An unprecedented sub-nanomolar affinity was found (Kd = 0.62 ± 0.33 nM) and applied to super-sensitive and red-emissive fluorescent staining of amyloid plaques in cortical brain tissue ex vivo. These fluorophores expand the dioxaborine-curcumin-based family of Aβ-sensitive fluorophores with a promising new imaging agent.
Keywords : β-Amyloid, Small-molecular fluorescent probe, Dioxaborine-dye, Hydrophobicity tailoring, Alzheimer's disease
논문정보
- Research article
- 2021년 11월 (BRIC 등록일 2021-11-12)
- 국내(교신)+국외 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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