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2018 (Engelska)Ingår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 24, nr 28, s. 7210-7216Artikel i tidskrift (Refereegranskat) Published
Abstract [en]
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 Alzheimers disease (AD) pathology comprising A beta 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 A beta 1-42 (13-300nmK(d)) and Tau (16-200nmK(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 A beta 1-42 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 A pathology found in human AD brain in a different mode compared with PiB, potentially recognizing different polymorphs of A fibrils.
Ort, förlag, år, upplaga, sidor
WILEY-V C H VERLAG GMBH, 2018
Nyckelord
Alzheimers disease; amyloid ligands; dyes/pigments; fluorescence; microscopy
Nationell ämneskategori
Organisk kemi
Identifikatorer
urn:nbn:se:liu:diva-148653 (URN)10.1002/chem.201800501 (DOI)000434074800013 ()29543355 (PubMedID)
Anmärkning
Funding Agencies|China Scholarship Council; Swedish Research Council [2015-04521]; Goran Gustafsson Foundation; Swedish Alzheimer Foundation; Swedish Brain foundation; Linkoping University (LiU-Neuro); NIH/NINDS [R21 NS080576]
2018-06-182018-06-182019-11-08