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Pentameric thiophene-based ligands that spectrally discriminate amyloid-β and tau aggregates display distinct solvatochromism and viscosity-induced spectral shifts.

Simon RA, Shirani H, Aslund KO, Bäck M, Haroutunian V, Gandy S, Nilsson KP - Chemistry (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Linköping University, 581 83 Linköping (Sweden).

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Related in: MedlinePlus

Chemical structures, Lippert–Mataga solvatochromism plots and viscosity plots of the pentameric LCOs: A) HS-72, B) p-FTAA, C) p-FTAA-Se, D) p-HTAA and E) p-FTAA-Ph. For the solvatochromism, solvents of increasing polarity in the following order: ethyl acetate, octanol, dimethyl sulfoxide (DMSO), ethylene glycol, methanol, and water were used. For the viscosity experiments, LCOs were mixed in solutions of ethylene glycol and glycerol with increasing concentrations of glycerol. The LCO concentration was 300 nm for all experiments.
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fig01: Chemical structures, Lippert–Mataga solvatochromism plots and viscosity plots of the pentameric LCOs: A) HS-72, B) p-FTAA, C) p-FTAA-Se, D) p-HTAA and E) p-FTAA-Ph. For the solvatochromism, solvents of increasing polarity in the following order: ethyl acetate, octanol, dimethyl sulfoxide (DMSO), ethylene glycol, methanol, and water were used. For the viscosity experiments, LCOs were mixed in solutions of ethylene glycol and glycerol with increasing concentrations of glycerol. The LCO concentration was 300 nm for all experiments.

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


Pentameric thiophene-based ligands that spectrally discriminate amyloid-β and tau aggregates display distinct solvatochromism and viscosity-induced spectral shifts.

Simon RA, Shirani H, Aslund KO, Bäck M, Haroutunian V, Gandy S, Nilsson KP - Chemistry (2014)

Chemical structures, Lippert–Mataga solvatochromism plots and viscosity plots of the pentameric LCOs: A) HS-72, B) p-FTAA, C) p-FTAA-Se, D) p-HTAA and E) p-FTAA-Ph. For the solvatochromism, solvents of increasing polarity in the following order: ethyl acetate, octanol, dimethyl sulfoxide (DMSO), ethylene glycol, methanol, and water were used. For the viscosity experiments, LCOs were mixed in solutions of ethylene glycol and glycerol with increasing concentrations of glycerol. The LCO concentration was 300 nm for all experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4221846&req=5

fig01: Chemical structures, Lippert–Mataga solvatochromism plots and viscosity plots of the pentameric LCOs: A) HS-72, B) p-FTAA, C) p-FTAA-Se, D) p-HTAA and E) p-FTAA-Ph. For the solvatochromism, solvents of increasing polarity in the following order: ethyl acetate, octanol, dimethyl sulfoxide (DMSO), ethylene glycol, methanol, and water were used. For the viscosity experiments, LCOs were mixed in solutions of ethylene glycol and glycerol with increasing concentrations of glycerol. The LCO concentration was 300 nm for all experiments.
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

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Linköping University, 581 83 Linköping (Sweden).

Show MeSH
Related in: MedlinePlus