Electrochemical features of the interaction between (R)-/(S)-methyl-2- (5-fluorouracil-1-acetamide)-3-phenylpropionate and DNAs

ABSTRACT

Cyclic voltammetry was exploited to understand the interaction between chiral methyl-2-(5- fluorouracil-1-acetamide)-3-phenylpropionate molecules (denoted as (R)- or (S)-5FUPPM) and double-stranded (ds) or G-quadruplex (G4) DNAs. Using Fe(CN)63- as the redox mark, experiments illustrate that the anodic peak of Fe(CN)63- oxidation decreases as the concentration of 5FUPPM in the solution is increased. Calculation with the Langmuir equation yields the binding equilibrium constant of 9.1 × 103 for the dsDNA and (S)-5FUPPM and of 3.3 × 103 for dsDNA and (R)-5FUPPM, suggesting that (S)-5FUPPM has more favorable interaction with dsDNA. On the other hand, the calculated binding constant between G4-DNA and (S)-5FUPPM is 1.6 × 104, as opposed to 3.2 × 104 between G4-DNA and (R)-5FUPPM. The results suggest that the binding selectivity of (R)-5FUPPM with DNAs, defined with (KG4-DNA/KdsDNA), is about 5 times larger than that of (S)-5FUPPM and DNAs, which is consistent with their inhibition rate on tumor cell. The information achieved here suggests that electrochemical characterization can provide useful information for the screening of new drug candidates.