Characterizing inhibitors of human AP endonuclease 1
Fig 6
Evaluation of compounds 5, 6, and 7 for aggregation by DLS and for inhibition of APE1.
Autocorrelation functions from DLS are shown in panels a, d, and g for the compound in buffer that lacks (circle) or contains (triangle) detergent (0.05% Brij 35). Solid lines are controls for buffer alone (no compound) in the absence (black) or presence (grey) of detergent. Data for compounds in detergent-free buffer after centrifugation is indicated by red stars. Panels b, e, and h show scattering intensity (kilocounts per second) versus compound concentration for compounds in buffer that lacks (circles) or contains (triangles) detergent. Data for compounds in detergent-free buffer after centrifugation is indicated by red stars. Panels c, f, and i show fraction activity of APE1 in the presence of a given compound. Data for 5 are shown at a single concentration of 0.33 mM for reactions that included Brij 35 (0.05%) and BSA (0.1 mg/ml) (grey bar) or 100-fold lower concentrations of these components (white bar). The dependence of FA on compound concentration gives an IC50 of 3.1 ± 0.3 μM and slope of 1.5 ± 0.2 for 6, and an IC50 of 8.1 ± 0.6 μM and slope of 1.2 ± 0.1 for 7. Compounds were introduced to DLS samples or enzyme reactions from 100x stocks in DMSO, and compound-free control samples also contained 1% DMSO.