Fig. 1: Structural model of TbRPA1 DBD-A in complex with JC-229 and inhibition of T. brucei cell proliferation by JC-229.

a Schematic diagram of the three subunits that comprise human and T. brucei RPA complexes. Positions of amino acid residues defining each domain are shown. DBD DNA-binding domain and WH winged helix. b Left: The structure alignment of HsDBD-F (light blue) to TbRPA1 DBD-A (red) generated by Pymol software (SWISS-MODEL). Middle: X-ray co-crystal structure of HsDBD-F (light blue) in complex with ATRIP derived peptide (green) (PDB code: 4NB3). Right: A 3D homology model of TbRPA1 DBD-A (red) interacting with ssDNA (SWISS-MODEL). c Induced-fit docking model showing the binding position of JC-229 in the ssDNA-binding pocket of TbRPA1 DBD-A (ribbon (left) and sphere (right) models shown). d Synthesis scheme for JC-229. e Inhibition of T. brucei cell growth by JC-229. Wild-type (WT) T. brucei cells were treated with 50 µM JC-229 for 3 days and viability was determined using the AlamarBlue assay. Three biological replicates were used for each measurement (n = 3). Error bars indicate mean ± SD. f Dose-dependent growth inhibition of T. brucei by JC-229. T. brucei cells were treated with increasing concentrations of JC-229 (0.5 to 50 μM) for 72 h and viability was determined with the AlamarBlue assay. A standard 4-Parameter Logistic (4-PL) curve from GraphPad Prism software generated the EC₅₀ value. All growth experiments were performed in triplicate using biological replicates (n = 3). Error bars indicate mean ± SD. Source data are provided as a Source Data file.