Detection and Imaging of Aβ1-42 and Tau Fibrils by Redesigned Fluorescent X-34 Analogues.

Autor: Zhang J; Division of chemistry, Department of Physics, Chemistry and Biology, Linköping University, 581 83, Linköping, Sweden., Sandberg A; Division of chemistry, Department of Physics, Chemistry and Biology, Linköping University, 581 83, Linköping, Sweden., Konsmo A; Department of Physics, The Norwegian University of Science and Technology, 7491, Trondheim, Norway., Wu X; Division of chemistry, Department of Physics, Chemistry and Biology, Linköping University, 581 83, Linköping, Sweden., Nyström S; Division of chemistry, Department of Physics, Chemistry and Biology, Linköping University, 581 83, Linköping, Sweden., Nilsson KPR; Division of chemistry, Department of Physics, Chemistry and Biology, Linköping University, 581 83, Linköping, Sweden., Konradsson P; Division of chemistry, Department of Physics, Chemistry and Biology, Linköping University, 581 83, Linköping, Sweden., LeVine H 3rd; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536-0230, USA., Lindgren M; Division of chemistry, Department of Physics, Chemistry and Biology, Linköping University, 581 83, Linköping, Sweden.; Department of Physics, The Norwegian University of Science and Technology, 7491, Trondheim, Norway., Hammarström P; Division of chemistry, Department of Physics, Chemistry and Biology, Linköping University, 581 83, Linköping, Sweden.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2018 May 17; Vol. 24 (28), pp. 7210-7216. Date of Electronic Publication: 2018 Apr 26.
DOI: 10.1002/chem.201800501
Abstrakt: We revisited the Congo red analogue 2,5-bis(4'-hydroxy-3'-carboxy-styryl)benzene (X-34) to develop this highly fluorescent amyloid dye for imaging Alzheimer's disease (AD) pathology comprising Aβ and Tau fibrils. A selection of ligands with distinct optical properties were synthesized by replacing the central benzene unit of X-34, with other heterocyclic moieties. Full photophysical characterization was performed, including recording absorbance and fluorescence spectra, Stokes shift, quantum yield and fluorescence lifetimes. All ligands displayed high affinity towards recombinant amyloid fibrils of Aβ1-42 (13-300 nm K d ) and Tau (16-200 nm K d ) as well as selectivity towards the corresponding disease-associated protein aggregates in AD tissue. We observed that these ligands efficiently displaced X-34, but not Pittsburgh compound B (PiB) from recombinant Aβ1-42 amyloid fibrils, arguing for retained targeting of the Congo red type binding site. We foresee that the X-34 scaffold offers the possibility to develop novel high-affinity ligands for Aβ pathology found in human AD brain in a different mode compared with PiB, potentially recognizing different polymorphs of Aβ fibrils.
(© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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