Targeting the OB-Folds of Replication Protein A with Small Molecules
Figure 4
Inhibition of full-length heterotrimeric RPA but not DBD-A/B-DNA-binding activity by the MCI13 series of bicyclic isoborneol haloesters. The control used is a distillate of the reaction components of the synthesis of the MCI13 compounds diluted in equal concentration of DMSO as the MCI13, inhibitors. (a) Increasing concentrations of control compound, MCI13E, or MCI13F (25, 50, 100, and 200 μM) were titrated in DNA binding reactions containing full-length heterotrimeric RPA. Binding to [32P]-ss 30-base 3Pc3 DNA was assessed by EMSA as described in “Section 2.” (b) The same inhibitor concentrations were assessed in reactions measuring the binding of DBD-A/B to a 30-mer substrate. (c) Analysis of control, MCI13E, and MCI13F inhibition of full length RPA. Average of three independent experiments is shown with Standard Deviation as error bars. From this graph, IC50 were calculated. MCI13E had a calculated IC50 of μM, while MCI13F had a calculated IC50 of μM.
