Abstract
Protein misfolding diseases are characterized by deposition of protein aggregates, and optical ligands for molecular characterization of these disease-associated structures are important for understanding their potential role in the pathogenesis of the disease. Luminescent conjugated oligothiophenes (LCOs) have proven useful for optical identification of a broader subset of disease-associated protein aggregates than conventional ligands, such as thioflavin T and Congo red. Herein, the molecular requirements for achieving LCOs able to detect nonthioflavinophilic Aβ aggregates or non-congophilic prion aggregates, as well as spectrally discriminate Aβ and tau aggregates, were investigated. An anionic pentameric LCO was subjected to chemical engineering by: 1) replacing thiophene units with selenophene or phenylene moieties, or 2) alternating the anionic substituents along the thiophene backbone. In addition, two asymmetric tetrameric ligands were generated. Overall, the results from this study identified conformational freedom and extended conjugation of the conjugated backbone as crucial determinants for obtaining superior thiophene-based optical ligands for sensitive detection and spectral assignment of disease-associated protein aggregates.
Highlights
Accumulation of protein deposits, so called amyloid, is the histopathological hallmark of several devastating diseases[1,2] and the development of sensitive optical ligands to detect and characterize these disease-associated structures is of great interest
From the histology experiments, the level of conformational freedom along the conjugated backbone was identified as a novel criterion for spectral separation of Aβ aggregates and neurofibrillary tangles (NFTs)
We have verified and identified distinct molecular requirements that are highly important to achieve thiophene-based ligands that are superior compared to conventional ligands for optical assignment of disease-associated protein aggregates
Summary
Accumulation of protein deposits, so called amyloid, is the histopathological hallmark of several devastating diseases[1,2] and the development of sensitive optical ligands to detect and characterize these disease-associated structures is of great interest.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
