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Distinct Heterocycl...
Distinct Heterocyclic Moieties Govern the Selectivity of Thiophene‐Vinylene‐Based Ligands towards Aβ or Tau Pathology in Alzheimer's Disease
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- Björk, Linnea (författare)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Shirani, Hamid (författare)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Todarwal, Yogesh (författare)
- KTH,Teoretisk kemi och biologi,Patrick Norman,KTH Royal Inst Technol, Sweden
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- Linares, Mathieu, 1979- (författare)
- KTH,Teoretisk kemi och biologi,KTH Royal Inst Technol, Sweden
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- Vidal, Ruben (författare)
- Department of Pathology and Laboratory Medicine Indiana University School of Medicine Indianapolis 46202 Indiana USA,Indiana Univ Sch Med, IN 46202 USA
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- Ghetti, Bernardino (författare)
- Department of Pathology and Laboratory Medicine Indiana University School of Medicine Indianapolis 46202 Indiana USA,Indiana Univ Sch Med, IN 46202 USA
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- Norman, Patrick (författare)
- KTH,Teoretisk kemi och biologi,KTH Royal Inst Technol, Sweden
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- Klingstedt, Therése (författare)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Nilsson, K. Peter R. (författare)
- Linköpings universitet,Kemi,Tekniska fakulteten
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(creator_code:org_t)
- Wiley, 2023
- 2023
- Engelska.
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Ingår i: European Journal of Organic Chemistry. - : Wiley. - 1434-193X .- 1099-0690. ; 26:41, s. e202300583-
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Distinct 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 Alzheimer'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.
Ämnesord
- NATURVETENSKAP -- Kemi -- Teoretisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Theoretical Chemistry (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- Alzheimer's disease
- amyloid-β
- fluorescent ligands
- protein aggregates
- tau
- Kemi
- Chemistry
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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