Mangiferin binding to serum albumin is non-saturable and induces conformational changes at high concentrations

The binding interaction between mangiferin (MGF), which a natural xanthone isolated from mangoes, and bovine serum albumin (BSA) was studied with absorbance and fluorescence spectroscopy, cyclic voltammetry and molecular modeling. The data were analyzed to assess the binding mechanism, effect of pH and ionic strength, conformational changes in the protein and electrical charge transfer involved. The MGF–BSA complex exhibited positive cooperativity with a 1:1 stoichiometry (Kd=0.38 mmol L−1) for the first binding site and a non-saturable binding at high ligand concentrations. Furthermore, the data also suggest an increase in drug bioavailability in the acidic region and relatively low ionic strength values, which are close to physiological levels. The data suggest a specific electrostatic interaction together with hydrophobic effects and H-bonding displayed in MGF binding to the BSA IIA subdomain. Synchronous fluorescence spectra indicate that there are conformational changes in the polypeptide backbone upon ligand binding. Cyclic voltammetry indicates that there is an irreversible charge transfer between MGF and BSA that is modulated by diffusion on the electrode surface, where two electrons are transferred. These results can help the knowledge of the pharmacokinetic activities of natural or chemical xanthone-based drugs. - Highlights: ► The MGF–BSA complex exhibited positive cooperativity beyond 1:1 stoichiometry. ► The interaction of MGF with BSA is non-saturable at higher ligand concentration. ► The binding was accomplished by H-bonding, hydrophobic and electrostatic forces. ► The apparent binding constant for MGF–BSA was 0.38 mmol L−1. ► MGF binds electrostatically to BSA, different from a hydrophobic interaction to HSA.