A Difluoroboron beta-Diketonate Probe Shows "Turn-on" Near-Infrared Fluorescence Specific for Tau Fibrils

Title
A Difluoroboron beta-Diketonate Probe Shows "Turn-on" Near-Infrared Fluorescence Specific for Tau Fibrils
Authors
추현아류훈현승재박광수김미경서유진하태웅유경하황유진이정희정유훈
Keywords
Alzheimer’s disease; tau-specific probe; fluorescence imaging; molecular rotor
Issue Date
2017-10
Publisher
ACS Chemical Neuroscience
Citation
VOL 8, NO 10-2131
Abstract
Tau aggregation in neuronal cells has recently received significant attention as a robust predictor of the progression of Alzheimers disease (AD) because of its proven correlation with the degree of cognitive impairment in AD patients. Accordingly, noninvasive imaging of tau aggregates has been highlighted as a promising diagnostic tool for AD. We have previously identified a tau-specific turn-on near-infrared fluorescent (NIRF) probe (1), and, in this study, structural modification was performed to optimize its physicochemical as well as fluorescence properties. Thus, a series of fluorescent dyes (2a-2j) composed of a variously substituted difluoroboron beta-diketonate and an N,N-dimethylaniline moiety linked by a length-extendable pi-bridge were prepared. Among those, isobutyl-substituted difluoroboron beta-ketonate with a pi-conjugated 1,4-butadienyl linker (2e) showed the most promising properties as a tau-specific NIRF probe. Compared with 1, the turn-on fluorescence of 2e was more specific to tau fibrils, and it showed 8.8- and 6.2-times higher tau-over-A beta and tau-over-BSA specificity, respectively. Also, the fluorescence intensity of 2e upon binding to tau fibrils was substantially higher (similar to 2.9 times) than that observed from 1. The mechanism for tau-specificity of 2e was investigated, which suggested that the molecular rotor-like property of 2e enables specific recognition of the microenvironment of tau aggregates to emit strong fluorescence. In transgenic cell lines stably expressing GFP-tagged tau proteins, 2e showed good colocalization with tau-GFP. Moreover, the fluorescence from 2e exhibited almost complete overlap with p-Tau antibody staining in the human AD brain tissue section. Collectively, these observations demonstrate the potential of 2e as a tau-specific fluorescent dye in both in vitro and ex vivo settings.
URI
http://pubs.kist.re.kr/handle/201004/66342
ISSN
1948-7193
Appears in Collections:
KIST Publication > Article
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE