Search

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. [ABSTRACT FROM AUTHOR]

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 can be utilized for spectral assignment of different morphotypes of β-amyloid or tau aggregates present in transgenic mice at distinct ages. The ability of the ligand to spectrally distinguish between the aggregated morphotypes was reduced when the spacing between the anionic substituents along the conjugated thiophene backbone was altered, which verified that specific molecular interactions between the ligand and the protein aggregate are necessary to detect aggregate polymorphism. Our findings provide the structural and functional basis for the development of new fluorescent ligands that can distinguish between different morphotypes of protein aggregates. [ABSTRACT FROM AUTHOR]

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 proven useful for spectral discrimination of amyloid-beta (Aβ) and tau neurofibrillary tangles (NFTs), two of the pathological hallmarks associated with Alzheimer's disease. Herein, the solvatochromism of a library of anionic pentameric thiophene-based ligands, as well as their ability to spectrally discriminate Aβ and tau aggregates, were investigated. Overall, the results from this study identified distinct solvatochromic and viscosity-dependent behavior of thiophene-based ligands that can be applied as indices to direct the chemical design of improved LCOs for spectral separation of Aβ and tau aggregates in brain tissue sections. The results also suggest that the observed spectral transitions of the ligands are due to their ability to conform by induced fit to specific microenvironments within the binding interface of each particular protein aggregate. We foresee that these findings might aid in the chemical design of thiophene-based ligands that are increasingly selective for distinct disease-associated protein aggregates. [ABSTRACT FROM AUTHOR]

The development of chiral optoelectronic materials is of great interest due to their potential of being utilized in electronic devices, biosensors, and artificial enzymes. Herein, we report the chiral-optical properties and architectural arrangement of optoelectronic materials generated from noncovalent self-assembly of a cationic synthetic peptide and five chemically defined anionic pentameric oligothiophenes. The peptide-oligothiophene hybrid materials exhibit a three-dimensional ordered helical structure and optical activity in the Π-Π* transition region that are observed due to a single chain induced chirality of the conjugated thiophene backbone upon interaction with the peptide. The latter property is highly dependent on electrostatic interactions between the peptide and the oligothiophene, verifying that a distinct spacing of the carboxyl groups along the thiophene backbone is a major chemical determinant for having a hybrid material with distinct optoelectronic properties. The necessity of the electrostatic interaction between specific carboxyl functionalities along the thiophene backbone and the lysine residues of the peptide, as well as the induced circular dichroism of the thiophene backbone, was also confirmed by theoretical calculations. We foresee that our findings will aid in designing optoelectronic materials with dynamic architectonical precisions as well as offer the possibility to create the next generation of materials for organic electronics and organic bioelectronics. [ABSTRACT FROM AUTHOR]