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Synthesis of Thiophene-Based Optical Ligands That Selectively Detect Tau Pathology in Alzheimers Disease
Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
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2017 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 23, no 67, p. 17127-17135Article in journal (Refereed) Published
Abstract [en]

The accumulation of protein aggregates is associated with many devastating neurodegenerative diseases and the development of molecular ligands able to detect these pathological hallmarks is essential. Here, the synthesis of thiophene based optical ligands, denoted bi-thiophene-vinyl-benzothiazoles (bTVBTs) that can be utilized for selective assignment of tau aggregates in brain tissue with Alzheimers disease (AD) pathology is reported. The ability of the ligands to selectively distinguish tau deposits from the other AD associated pathological hallmark, senile plaques consisting of aggregated amyloid- (A) peptide, was reduced when the chemical composition of the ligands was altered, verifying that specific molecular interactions between the ligands and the aggregates are necessary for the selective detection of tau deposits. Our findings provide the structural and functional basis for the development of new fluorescent ligands that can distinguish between aggregated proteinaceous species consisting of different proteins. In addition, the bTVBT scaffold might be utilized to create powerful practical research tools for studying the underlying molecular events of tau aggregation and for creating novel agents for clinical imaging of tau pathology in AD.

Place, publisher, year, edition, pages
WILEY-V C H VERLAG GMBH , 2017. Vol. 23, no 67, p. 17127-17135
Keywords [en]
Alzheimers disease; amyloid-beta; fluorescent ligands; protein aggregates; tau aggregates
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-144458DOI: 10.1002/chem.201703846ISI: 000418570000028PubMedID: 28926133OAI: oai:DiVA.org:liu-144458DiVA, id: diva2:1176568
Note

Funding Agencies|Swedish Foundation for Strategic Research; Erling Persson Foundation; Swedish Research Council; NIH [P50AG05681, 5PO1-AG03991]

Available from: 2018-01-22 Created: 2018-01-22 Last updated: 2018-02-15

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