title: Anionic Oligothiophenes Compete for Binding of X-34 but not PIB to Recombinant Aβ Amyloid Fibrils and Alzheimer's Disease Brain-Derived Aβ.
abstract: Deposits comprised of amyloid-β (Aβ) are one of the pathological hallmarks of Alzheimer's 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 compound B (PIB) from recombinant Aβ amyloid fibrils and Alzheimer's disease brain-derived Aβ. Overall, we foresee that the oligothiophene scaffold offers the possibility to develop novel high-affinity ligands for Aβ pathology only found in human AD brain, targeting a different site than PIB.
authors: Division of Chemistry, Department of Physics, Chemistry and Biology, Linköping University, 581 83, Linköping, Sweden.
authors: Marcus
authors: M
authors: Bäck
authors: Division of Chemistry, Department of Physics, Chemistry and Biology, Linköping University, 581 83, Linköping, Sweden.
authors: Hanna
authors: H
authors: Appelqvist
authors: Department Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536-0230, USA.
authors: Harry
authors: H
authors: LeVine
authors: Division of Chemistry, Department of Physics, Chemistry and Biology, Linköping University, 581 83, Linköping, Sweden.
authors: K Peter R
authors: http://orcid.org/0000-0002-5582-140X
authors: KP
authors: Nilsson
mesh_terms: D000475:Alkenes / Q000737:chemistry* / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D000814:Aniline Compounds / Q000737:chemistry* / Q000378:metabolism; D001565:Benzoates / Q000737:chemistry* / Q000378:metabolism; D001921:Brain / Q000473:pathology*; D006801:Humans; D049268:Positron-Emission Tomography; D013844:Thiazoles / Q000737:chemistry* / Q000378:metabolism; D013876:Thiophenes / Q000737:chemistry / Q000378:metabolism*
chemical_list: C413183:1,4-bis(3-carboxy-4-hydroxyphenylethenyl)-benzene; C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000475:Alkenes; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D001565:Benzoates; D013844:Thiazoles; D013876:Thiophenes
keywords: Alzheimer's disease; amyloid ligands; fluorescence; luminescent conjugated oligothiophenes; proteins