Fig. 4. Structural optimization of oligo-NSA to improve binding affinity and membrane permeability. (a) Chemical structures of substituents at R1, R3, and R5 and Ki values of compounds 1–4. Ki values were determined by a competitive FP assay using fluorescently labeled PMI peptide and MDM2. (b) Chemical structures of substituents at R2 and R4, A log P values, Pe values, and Ki values of compounds 4–9. A log P values are indices of lipophilicity of compounds. Pe values were determined by a Caco-2 assay. Ki values were determined by a competitive FP assay using fluorescently labeled PMI peptide and MDM2. n.d.: not determined due to low water solubility in aqueous solution. *p < 0.05 compared with compound 4.
