Fig. 2: Identification and characterization of the potent antagonist of αS aggregation using the 2D-FAST. | Nature Communications

Fig. 2: Identification and characterization of the potent antagonist of αS aggregation using the 2D-FAST.

From: Protein mimetic 2D FAST rescues alpha synuclein aggregation mediated early and post disease Parkinson’s phenotypes

Fig. 2

The graphical representation of the ThT intensity of 100 µM αS aggregation for four days in the absence and presence of monopyridyls (a), dipyridyls (e), and tripyridyls (k) at an equimolar ratio. The arrow indicates the most potent antagonist of αS aggregation. The generic chemical structures of monopyridyls (b), dipyridyls (f), and tripyridyls (l). The most potent monopyridyls (c), dipyridyls (g), and tripyridyls (m) antagonists of αS aggregation. SDS-PAGE gel shift assay analysis of 100 µM αS aggregation after four days in the absence and presence of monopyridyls (d) and dipyridyls/tripyridyls (q) at the indicated molar ratios. Gel image is representative of 3 individual experiments. The aggregation profile of 100 µM αS in the absence and presence of NS55 (h) and NS132 (n) at an equimolar ratio. TEM images of 100 µM αS aggregated for four days in the absence (i, o) and presence of equimolar NS55 (j) and NS132 (p). TEM images are representative of 3 individual experiments. r The ThT intensity of αS aggregation after four days in the absence and presence of NS132 derivatives. s Chemical structures of NS132 derivatives. t The ITC thermogram for the titration of NS132 into αS where heat burst curves and the corrected injection heats upper and lower panel, respectively. u Graphical presentation of the relative volume changes (V = volume change, V0 = total volume) of the backbone amide peaks of 15N-labeled αS (70 µM) in the presence of equimolar NS132. The colored sequences (blue and green) are the potential binding sites of NS132 on αS. The dashed line represents the reported volume changes in 15N-labeled αS residue peaks in the presence of NS132 above 5%. The ThT experiments were conducted three times and the reported change in the ThT intensity was an average of three separate experiments. The data were expressed as mean values ± SD. P values were determined by one-way ANOVA with Tukey’s multiple comparisons test where relevant. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Source data are provided as a Source Data file.

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