Fig. 1: Characterization of the antagonist activity of SK-129 against αS aggregation.
From: Foldamers reveal and validate therapeutic targets associated with toxic α-synuclein self-assembly
a The generic chemical structure of the OQ with Ri and Rj are the side chain surface functionalities. The side and top view of the crystal structure of OQs and the surface functionalities are represented by arrows. The OQs with the indicated side chains (Ri and Rj) were used in the study. c Chemical structure of SK-129 and the four side chains were indicated from 1 to 4. d The average of ThT-dye fluorescence-based aggregation profile of 100 µM αS in the absence and presence of SK-129 at the indicated molar ratios. The data were expressed as mean and the error bars report the S.D. (n = 3 independent experiments). e The chemical structures of the side chains at position 1 and 3 of various analogs of SK-129. f The antagonist activities of the analogs (100 μM) of SK-129 against 100 μM αS aggregation. The data were expressed as mean and the error bars report the s.e.m. (n = 3 independent experiments and each n consisted of 3 technical replicates). g The fit for the FP titration curve to determine the binding affinity between 10 μM SK-129F and αS. The chemical structure of SK-129F is shown as well. The data were expressed as mean and the error bars report the s.d. (n = 3 independent experiments). h The statistical analysis of the relative viability of SH-SY5Y cells when treated with the aggregated solution of 10 μM αS in the absence and presence of SK-129 at the indicated molar ratios. The data were expressed as mean and the error bars report the s.e.m. (n = 4 independent cell toxicity experiments and each n consisted of 4 technical replicates). i Confocal images of HEK cells treated with the aggregated solution of 7 μM αS in the absence and presence of SK-129 at an equimolar ratio. Inclusions of αSA53T-YFP = white arrows, Hoechst (blue), merge = Hoechst and αSA53T-YFP. j The flow cytometry-based analysis of HEK cells treated with the aggregated solution of 7 μM αS in the absence and presence of SK-129 at an equimolar ratio. The x-axis represents αSA53T-YFP aggregates containing cells that are stained with Proteostat dye (λ = 640 nm) and the y-axis represents the total number of cells with YFP (λ = 490 nm). k Columns A and B represent the relative % of HEK cells without and with αSA53T-YFP aggregates, respectively. l The number of αSA53T-YFP inclusions when HEK cells were treated with the aggregated solution of 7 μM αS in the absence and presence of SK-129 at an equimolar ratio. A total of 100 HEK cells were examined to count the number of inclusions at four different locations in the eight-well plate for each experiment and it was repeated in four independent experiments. The relative intensity of Proteostat dye-stained aggregates of αSA53T-YFP inclusions (m) and relative viability (n) of HEK cells treated with the aggregated solution of 7 μM αS in the absence and presence of SK-129 at an equimolar ratio. The data (for l–n) were expressed as mean and the error bars report the s.e.m. (n = 4 independent HEK cells-based experiments and each n consisted of four technical replicates). The statistical analysis was performed using one-way analysis of variance (ANOVA) with Tukey’s multiple comparison test. *p < 0.05, **p < 0.01, ***p < 0.001. Source data are provided as a Source Data file.
