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. Author manuscript; available in PMC: 2013 Sep 1.
Published in final edited form as: Biochimie. 2012 May 29;94(9):1974–1981. doi: 10.1016/j.biochi.2012.05.020

Figure 2. 4-aminoquinoline 1 exhibits mixed inhibition of bt-TG6 binding to TDP-43 using AlphaScreen® technology.

Figure 2

TDP-43 (0.1 nM) and 10 μg/mL of both streptavidin donor beads and anti-GST acceptor beads were incubated with various concentrations of biotinylated-TG6 (bt-TG6) and 1 for 3 hr at room temperature as described in section 2.2. (A) Saturation binding isotherms of bt-TG6 binding to TDP-43 in the absence (○), and presence of 1.0 μM (□), 3.2 μM (△), or 10 μM (◇) of 1. Data fit best to the mixed model inhibition equation compared to competitive inhibition equation (P < 0.01) in Graph Pad Prism® with a Ki value of 0.61 μM and α value of 7.0. (B) Dose-response curves for 1 in the presence of 0.32 nM (◇), 1.0 nM (△), 3.2 nM (□), 10 nM (○) bt-TG6. (C) Linear regression of pIC50 values from (B) vs log [bt-TG6] yields a slope of 0.51. Data represent mean ± S.E.M. of 4 determinations.