Seo, Yujin Park, Kwang-su Ha, Taewoong Kim, Mi Kyoung Hwang, Yu Jin Lee, Junghee Ryu, Hoon Choo, Hyunah Chong, Youhoon 2024-01-20T03:02:48Z 2024-01-20T03:02:48Z 2021-09-04 2016-11 1948-7193 https://pubs.kist.re.kr/handle/201004/123512 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-pi-acceptor architecture of the smart NIRF A beta 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 A beta fibrils (lambda(em)= 650 nm, Stokes shifts = 70-110 nm). In particular, combination of the 3,5-dirnethoxy-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 A beta= 5.7 and 3.8); they showed much higher fluorescence intensities upon binding to tau aggregates (FItau = 49 and 108) than when bound to A beta fibrils (FIA beta = 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. English AMER CHEMICAL SOC POSITRON-EMISSION-TOMOGRAPHY ASSOCIATION WORKGROUPS DIAGNOSTIC GUIDELINES NATIONAL INSTITUTE NEUROFIBRILLARY PATHOLOGY MOLECULAR PROBE RECOMMENDATIONS PET PREDICTION PLAQUES A Smart Near-Infrared Fluorescence Probe for Selective Detection of Tau Fibrils in Alzheimer's Disease Article 10.1021/acschemneuro.6b00174 1 ACS CHEMICAL NEUROSCIENCE, v.7, no.11, pp.1474 - 1481 ACS CHEMICAL NEUROSCIENCE 7 11 1474 1481 scie scopus 000388433000003 2-s2.0-84996503685 Biochemistry & Molecular Biology Chemistry, Medicinal Neurosciences Biochemistry & Molecular Biology Pharmacology & Pharmacy Neurosciences & Neurology Article POSITRON-EMISSION-TOMOGRAPHY ASSOCIATION WORKGROUPS DIAGNOSTIC GUIDELINES NATIONAL INSTITUTE NEUROFIBRILLARY PATHOLOGY MOLECULAR PROBE RECOMMENDATIONS PET PREDICTION PLAQUES Near-infrared fluorescence (NIRF) smart probe tau fibrils molecular rotor Alzheimer&apos s disease