Distinct Heterocyclic Moieties Govern the Selectivity of Thiophene-Vinylene-Based Ligands Towards Aβ or Tau Pathology in Alzheime’s Disease

dc.contributor.authorBjörk, Linnea
dc.contributor.authorShirani, Hamid
dc.contributor.authorTodarwal, Yogesh
dc.contributor.authorLinares, Mathieu
dc.contributor.authorVidal, Ruben
dc.contributor.authorGhetti, Bernardino
dc.contributor.authorNorman, Patrick
dc.contributor.authorKlingstedt, Therése
dc.contributor.authorNilsson, K. Peter R.
dc.contributor.departmentPathology and Laboratory Medicine, School of Medicine
dc.date.accessioned2024-12-09T16:05:57Z
dc.date.available2024-12-09T16:05:57Z
dc.date.issued2023
dc.description.abstractDistinct aggregated proteins are correlated with numerous neurodegenerative diseases and the development of ligands that selectively detect these pathological hallmarks is vital. Recently, the synthesis of thiophene-based optical ligands, denoted bi-thiophene-vinyl-benzothiazoles (bTVBTs), that could be utilized for selective assignment of tau pathology in brain tissue with Alzheime's disease (AD) pathology, was reported. Herein, we investigate the ability of these ligands to selectively distinguish tau deposits from aggregated amyloid-β (Aβ), the second AD associated pathological hallmark, when replacing the terminal thiophene moiety with other heterocyclic motifs. The selectivity for tau pathology was reduced when introducing specific heterocyclic motifs, verifying that specific molecular interactions between the ligands and the aggregates are necessary for selective detection of tau deposits. In addition, ligands having certain heterocyclic moieties attached to the central thiophene-vinylene building block displayed selectivity to aggregated Aβ pathology. Our findings provide chemical insights for the development of ligands that can distinguish between aggregated proteinaceous species consisting of different proteins and might also aid in creating novel agents for clinical imaging of tau pathology in AD.
dc.eprint.versionAuthor's manuscript
dc.identifier.citationBjörk L, Shirani H, Todarwal Y, et al. Distinct Heterocyclic Moieties Govern the Selectivity of Thiophene-Vinylene-Based Ligands Towards Aβ or Tau Pathology in Alzheime's Disease. European J Org Chem. 2023;26(41):e202300583. doi:10.1002/ejoc.202300583
dc.identifier.urihttps://hdl.handle.net/1805/44854
dc.language.isoen_US
dc.publisherWiley
dc.relation.isversionof10.1002/ejoc.202300583
dc.relation.journalEuropean Journal of Organic Chemistry
dc.rightsPublisher Policy
dc.sourcePMC
dc.subjectAlzheime’s disease
dc.subjectAmyloid-β
dc.subjectFluorescent ligands
dc.subjectProtein aggregates
dc.subjectTau
dc.titleDistinct Heterocyclic Moieties Govern the Selectivity of Thiophene-Vinylene-Based Ligands Towards Aβ or Tau Pathology in Alzheime’s Disease
dc.typeArticle
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