A Smart Near-Infrared Fluorescence Probe for Selective Detection of Tau Fibrils in Alzheimer's Disease

Title
A Smart Near-Infrared Fluorescence Probe for Selective Detection of Tau Fibrils in Alzheimer's Disease
Authors
추현아류훈서유진박광수하태웅김미경황유진이정희정유훈
Keywords
Near-infrared fluorescence; smart probe; tau fibrils; molecular rotor; Alzheimer’s disease
Issue Date
2016-11
Publisher
ACS Chemical Neuroscience
Citation
VOL 7, NO 11-1481
Abstract
Development of a novel, tau-selective smart near-infrared fluorescence (NIRF) probe was attempted by combining the previously identified core scaffold 3,5-dimethoxy-N,N-dimethylaniline-4-yl moiety, with the characteristic donor-π-acceptor architecture of the smart NIRF Aβ probes DANIR-2c and MCAAD-3. A series of compounds (2 and 3) were prepared, which were identified as “turn-on” NIRF probes for the visual detection of tau aggregates and Aβ fibrils (λem = 650 nm, Stokes shifts = 70– 110 nm). In particular, combination of the 3,5-dimethoxy-N,N-dimethylanilin-4-yl moiety and the donor part of MCAAD-3 endowed the resulting probes, 3g and 3h, with significant selectivity toward tau aggregates (selectivity for tau over Aβ = 5.7 and 3.8); they showed much higher fluorescence intensities upon binding to tau aggregates (FItau = 49 and 108) than when bound to Aβ fibrils (FIAβ = 9 and 28). Quantitative analysis of binding affinities and fluorescence properties of 3g and 3h revealed that microenvironment-sensitive molecular rotor-like behavior, rather than binding affinity to the target, is responsible for their selective turn-on fluorescence detection of tau fibrils. Selective fluorescent labeling of tau fibrils by 3g and 3h was further demonstrated by immunofluorescence staining of human Alzheimer’s disease brain sections, which showed colocalization of the probes (3g and 3h) and phosphorylated tau antibody.
URI
http://pubs.kist.re.kr/handle/201004/64876
ISSN
1948-7193
Appears in Collections:
KIST Publication > Article
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