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dc.contributor.authorPark, Kwang-su-
dc.contributor.authorKim, Mi Kyoung-
dc.contributor.authorSeo, Yujin-
dc.contributor.authorHa, Taewoong-
dc.contributor.authorYoo, Kyeongha-
dc.contributor.authorHyeon, Seung Jae-
dc.contributor.authorHwang, Yu Jin-
dc.contributor.authorLee, Junghee-
dc.contributor.authorRyu, Hoon-
dc.contributor.authorChoo, Hyunah-
dc.contributor.authorChong, Youhoon-
dc.date.accessioned2024-01-20T00:32:11Z-
dc.date.available2024-01-20T00:32:11Z-
dc.date.created2021-09-03-
dc.date.issued2017-10-
dc.identifier.issn1948-7193-
dc.identifier.urihttps://pubs.kist.re.kr/handle/201004/122255-
dc.description.abstractTau 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.-
dc.languageEnglish-
dc.publisherAMER CHEMICAL SOC-
dc.subjectALZHEIMERS-DISEASE-
dc.subjectAMYLOID PLAQUES-
dc.subjectIMAGING PROBES-
dc.subjectNEUROFIBRILLARY PATHOLOGY-
dc.subjectSELECTIVE DETECTION-
dc.subjectMOLECULAR PROBE-
dc.subjectPET-
dc.subjectSPECTROSCOPY-
dc.subjectTANGLES-
dc.subjectCELLS-
dc.titleA Difluoroboron beta-Diketonate Probe Shows "Turn-on" Near-Infrared Fluorescence Specific for Tau Fibrils-
dc.typeArticle-
dc.identifier.doi10.1021/acschemneuro.7b00224-
dc.description.journalClass1-
dc.identifier.bibliographicCitationACS CHEMICAL NEUROSCIENCE, v.8, no.10, pp.2124 - 2131-
dc.citation.titleACS CHEMICAL NEUROSCIENCE-
dc.citation.volume8-
dc.citation.number10-
dc.citation.startPage2124-
dc.citation.endPage2131-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
dc.identifier.wosid000413502700006-
dc.identifier.scopusid2-s2.0-85031676952-
dc.relation.journalWebOfScienceCategoryBiochemistry & Molecular Biology-
dc.relation.journalWebOfScienceCategoryChemistry, Medicinal-
dc.relation.journalWebOfScienceCategoryNeurosciences-
dc.relation.journalResearchAreaBiochemistry & Molecular Biology-
dc.relation.journalResearchAreaPharmacology & Pharmacy-
dc.relation.journalResearchAreaNeurosciences & Neurology-
dc.type.docTypeArticle-
dc.subject.keywordPlusALZHEIMERS-DISEASE-
dc.subject.keywordPlusAMYLOID PLAQUES-
dc.subject.keywordPlusIMAGING PROBES-
dc.subject.keywordPlusNEUROFIBRILLARY PATHOLOGY-
dc.subject.keywordPlusSELECTIVE DETECTION-
dc.subject.keywordPlusMOLECULAR PROBE-
dc.subject.keywordPlusPET-
dc.subject.keywordPlusSPECTROSCOPY-
dc.subject.keywordPlusTANGLES-
dc.subject.keywordPlusCELLS-
dc.subject.keywordAuthorAlzheimer&apos-
dc.subject.keywordAuthors disease-
dc.subject.keywordAuthortau-specific probe-
dc.subject.keywordAuthorfluorescence imaging-
dc.subject.keywordAuthormolecular rotor-
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