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- Bäck, Marcus, et al.
(författare)
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Anionic Oligothiophenes Compete for Binding of X-34 but not PIB to Recombinant A beta Amyloid Fibrils and Alzheimers Disease Brain-Derived A beta
- 2016
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Ingår i: CHEMISTRY-A EUROPEAN JOURNAL. - : WILEY-V C H VERLAG GMBH. - 0947-6539. ; 22:51, s. 18335-18338
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Tidskriftsartikel (refereegranskat)abstract
- Deposits comprised of amyloid- (A) are one of the pathological hallmarks of Alzheimers disease (AD) and small hydrophobic ligands targeting these aggregated species are used clinically for the diagnosis of AD. Herein, we observed that anionic oligothiophenes efficiently displaced X-34, a Congo Red analogue, but not Pittsburgh compoundB (PIB) from recombinant A amyloid fibrils and Alzheimers disease brain-derived A. Overall, we foresee that the oligothiophene scaffold offers the possibility to develop novel high-affinity ligands for A pathology only found in human AD brain, targeting a different site than PIB.
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| 4. |
- LeVine III, Harry, et al.
(författare)
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Reporters of amyloid structural polymorphism
- 2014
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Ingår i: Bio-nanoimaging. - London : Academic Press. - 9780123944313 ; , s. 69-79
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Misfolding of proteins induced by environmental conditions or by the presence of destabilizing mutations often triggers squestration (aggresome formation) or cellular removal (unfolded protein response (UPR), autophagy) intracellular responses. Extracellular aggregates are phagocytosed or endocytosed by macrophages in the periphery and microglia and astrocytes in the brain and central nervous system. In some cases a highly stable altemative assembly structure, an amyloid fibril, is formed that is highly resistant to degadation and thus accumulates.
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| 6. |
- Zhang, Jun, et al.
(författare)
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Detection and Imaging of A beta 1-42 and Tau Fibrils by Redesigned Fluorescent X-34 Analogues
- 2018
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Ingår i: Chemistry - A European Journal. - : WILEY-V C H VERLAG GMBH. - 0947-6539 .- 1521-3765. ; 24:28, s. 7210-7216
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Zhang, Jun, Dr. 1987-, et al.
(författare)
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Intramolecular Proton and Charge Transfer of Pyrene-based trans-Stilbene Salicylic Acids Applied to Detection of Aggregated Proteins.
- 2018
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Ingår i: ChemPhysChem. - Weinheim, Germany : Wiley-VCH Verlag. - 1439-4235 .- 1439-7641. ; 19:22, s. 3001-3009
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Tidskriftsartikel (refereegranskat)abstract
- Two analogues to the fluorescent amyloid probe 2,5-bis(4'-hydroxy-3'-carboxy-styryl)benzene (X-34) were synthesized based on the trans-stilbene pyrene scaffold (Py1SA and Py2SA). The compounds show strikingly different emission spectra when bound to preformed Aβ1-42 fibrils. This remarkable emission difference is retained when bound to amyloid fibrils of four distinct proteins, suggesting a common binding configuration for each molecule. Density functional theory calculations show that Py1SA is twisted, while Py2SA is more planar. Still, an analysis of the highest occupied molecular orbitals (HOMOs) and lowest unoccupied molecular orbitals (LUMOs) of the two compounds indicates that the degree of electronic coupling between the pyrene and salicylic acid (SA) moieties is larger in Py1SA than in Py2SA. Excited state intramolecular proton transfer (ESIPT) coupled-charge transfer (ICT) was observed for the anionic form in polar solvents. We conclude that ICT properties of trans-stilbene derivatives can be utilized for amyloid probe design with large changes in emission spectra and decay times from analogous chemical structures depending on the detailed physical nature of the binding site.less thanbr /greater than (© 2018 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim.)
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