A Palette of Fluorescent Thiophene-Based Ligands for the Identification of Protein Aggregates
نویسندگان
چکیده
By replacing the central thiophene unit of an anionic pentameric oligothiophene with other heterocyclic moities, a palette of pentameric thiophene-based ligands with distinct fluorescent properties were synthesized. All ligands displayed superior selectivity towards recombinant amyloid fibrils as well as disease-associated protein aggregates in tissue sections.
منابع مشابه
The Structural Basis for Optimal Performance of Oligothiophene-Based Fluorescent Amyloid Ligands: Conformational Flexibility is Essential for Spectral Assignment of a Diversity of Protein Aggregates
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 p...
متن کاملSynthesis of a library of oligothiophenes and their utilization as fluorescent ligands for spectral assignment of protein aggregates.
Molecular probes for selective identification of protein aggregates are important to advance our understanding of the molecular pathogenesis underlying protein aggregation diseases. Here we report the chemical design of a library of anionic luminescent conjugated oligothiophenes (LCOs), which can be utilized as ligands for detection of protein aggregates. Certain molecular requirements were sho...
متن کاملDistinct Spacing Between Anionic Groups: An Essential Chemical Determinant for Achieving Thiophene-Based Ligands to Distinguish β-Amyloid or Tau Polymorphic Aggregates
The accumulation of protein aggregates is associated with many devastating neurodegenerative diseases and the existence of distinct aggregated morphotypes has been suggested to explain the heterogeneous phenotype reported for these diseases. Thus, the development of molecular probes able to distinguish such morphotypes is essential. We report an anionic tetrameric oligothiophene compound that c...
متن کاملFluorescent thiophene-based ligands for detection and characterization of disease-associated protein aggregates
In this thesis the unique optical properties of fluorescent ligands termed luminescent conjugated oligothiophenes (LCOs) have been used to study a variety of protein aggregates associated with human protein misfolding disease. This heterogeneous group of diseases contains well known and fatal members such as Alzheimer ́s and Huntington ́s disease and the development of sensitive tools for the det...
متن کاملPentameric Thiophene-Based Ligands that Spectrally Discriminate Amyloid-β and Tau Aggregates Display Distinct Solvatochromism and Viscosity-Induced Spectral Shifts
A wide range of neurodegenerative diseases are characterized by the deposition of multiple protein aggregates. Ligands for molecular characterization and discrimination of these pathological hallmarks are thus important for understanding their potential role in pathogenesis as well as for clinical diagnosis of the disease. In this regard, luminescent conjugated oligothiophenes (LCOs) have prove...
متن کامل