Pentameric thiophene-based ligands that spectrally discriminate amyloid-β and tau aggregates display distinct solvatochromism and viscosity-induced spectral shifts.
Bottom Line: 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.
Affiliation: Department of Chemistry, Linköping University, 581 83 Linköping (Sweden).Show MeSH
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Mentions: Solvatochromic behavior of small amyloid ligands can be used to approximate the amyloid fibril binding site polarity, as well as the relative change in the dipole moment for individual ligands.20–23 Therefore, we tested the solvatochromic behavior of a subset of previously reported anionic pentameric LCOs (Figure 1).11, 12, 171
Affiliation: Department of Chemistry, Linköping University, 581 83 Linköping (Sweden).