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Detection and Imaging of Aβ1‐42 and Tau Fibrils by Redesigned Fluorescent X‐34 Analogues
Author(s) -
Zhang Jun,
Sandberg Alexander,
Konsmo Audun,
Wu Xiongyu,
Nyström Sofie,
Nilsson K. Peter R.,
Konradsson Peter,
LeVine Harry,
Lindgren Mikael,
Hammarström Per
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201800501
Subject(s) - fluorescence , fibril , congo red , chemistry , amyloid (mycology) , quantum yield , recombinant dna , stokes shift , biophysics , crystallography , biochemistry , biology , organic chemistry , inorganic chemistry , physics , adsorption , quantum mechanics , gene
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 n m K d ) and Tau (16–200 n m 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.