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A Palette of Fluorescent Thiophene-Based Ligands for the Identification of Protein Aggregates.

Shirani H, Linares M, Sigurdson CJ, Lindgren M, Norman P, Nilsson KP - Chemistry (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Chemistry, Department of Physics, Chemistry and Biology, Linköping University, 581 83 Linköping (Sweden).

No MeSH data available.


Related in: MedlinePlus

Excitation- (left) and emission (right) spectra of HS-84 (A), HS-163 (B), HS-165 (C), HS-167 (D), and HS-169 (E) in PBS pH 7.4 (blue spectra) or mixed with recombinant Aβ 1-42 amyloid-like fibrils (red spectra). For HS-167 (D) and HS-169 (E) the purple and red emission spectra correlate to excitation at the first (377 nm) or second (510 or 536 nm) excitation maxima, respectively.
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fig02: Excitation- (left) and emission (right) spectra of HS-84 (A), HS-163 (B), HS-165 (C), HS-167 (D), and HS-169 (E) in PBS pH 7.4 (blue spectra) or mixed with recombinant Aβ 1-42 amyloid-like fibrils (red spectra). For HS-167 (D) and HS-169 (E) the purple and red emission spectra correlate to excitation at the first (377 nm) or second (510 or 536 nm) excitation maxima, respectively.

Mentions: In order to elucidate selective binding of the ligands to protein aggregates, all five ligands were tested towards amyloid-like fibrils made from recombinant Aβ 1-42 peptide. All of the ligands revealed distinct excitation and emission characteristics when bound to recombinant Aβ fibrils (Figure 2). When mixed with the amyloid-like fibrils, HS-84 (Figure 2 A), HS-163 (Figure 2 B), and HS-165 (Figure 2 C) displayed redshifted excitation spectra with resolved substructures, as well as blueshifted emission spectra with enhanced intensity and the characteristic double peaks reported for anionic oligothiophenes bound to recombinant amyloid-like fibrils.[10–13] HS-167 and HS-169 also display redshifted excitation maxima and blueshifted emission maxima when bound to Aβ 1-42 amyloid-like fibrils (Table S2 in the Supporting Information). In addition, a more pronounced enhancement of the emission intensity was observed from these d-A-D compounds upon interaction with the fibrils (Figure 2 D, E). Thus, similar to the most commonly used amyloid-specific dye, thioflavin T (ThT),[3, 27] HS-167 and 169 indicated a strong increase in fluorescence upon binding to amyloid fibrils. Overall, the five ligands provided distinct optical signatures upon binding to Aβ 1-42 fibrils, verifying that all of the ligands could be utilized for fluorescent assignment of recombinant amyloid-like fibrils.


A Palette of Fluorescent Thiophene-Based Ligands for the Identification of Protein Aggregates.

Shirani H, Linares M, Sigurdson CJ, Lindgren M, Norman P, Nilsson KP - Chemistry (2015)

Excitation- (left) and emission (right) spectra of HS-84 (A), HS-163 (B), HS-165 (C), HS-167 (D), and HS-169 (E) in PBS pH 7.4 (blue spectra) or mixed with recombinant Aβ 1-42 amyloid-like fibrils (red spectra). For HS-167 (D) and HS-169 (E) the purple and red emission spectra correlate to excitation at the first (377 nm) or second (510 or 536 nm) excitation maxima, respectively.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4641461&req=5

fig02: Excitation- (left) and emission (right) spectra of HS-84 (A), HS-163 (B), HS-165 (C), HS-167 (D), and HS-169 (E) in PBS pH 7.4 (blue spectra) or mixed with recombinant Aβ 1-42 amyloid-like fibrils (red spectra). For HS-167 (D) and HS-169 (E) the purple and red emission spectra correlate to excitation at the first (377 nm) or second (510 or 536 nm) excitation maxima, respectively.
Mentions: In order to elucidate selective binding of the ligands to protein aggregates, all five ligands were tested towards amyloid-like fibrils made from recombinant Aβ 1-42 peptide. All of the ligands revealed distinct excitation and emission characteristics when bound to recombinant Aβ fibrils (Figure 2). When mixed with the amyloid-like fibrils, HS-84 (Figure 2 A), HS-163 (Figure 2 B), and HS-165 (Figure 2 C) displayed redshifted excitation spectra with resolved substructures, as well as blueshifted emission spectra with enhanced intensity and the characteristic double peaks reported for anionic oligothiophenes bound to recombinant amyloid-like fibrils.[10–13] HS-167 and HS-169 also display redshifted excitation maxima and blueshifted emission maxima when bound to Aβ 1-42 amyloid-like fibrils (Table S2 in the Supporting Information). In addition, a more pronounced enhancement of the emission intensity was observed from these d-A-D compounds upon interaction with the fibrils (Figure 2 D, E). Thus, similar to the most commonly used amyloid-specific dye, thioflavin T (ThT),[3, 27] HS-167 and 169 indicated a strong increase in fluorescence upon binding to amyloid fibrils. Overall, the five ligands provided distinct optical signatures upon binding to Aβ 1-42 fibrils, verifying that all of the ligands could be utilized for fluorescent assignment of recombinant amyloid-like fibrils.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Chemistry, Department of Physics, Chemistry and Biology, Linköping University, 581 83 Linköping (Sweden).

No MeSH data available.


Related in: MedlinePlus