Structural and molecular aspects of flavonoids as ligands for serum transferrin.

Human serum transferrin (HST) acts as a carrier for Fe3+ and other ions. Binding of flavonoids to HST produces changes in the protein structure with direct implication on iron delivery into cells. We investigate the binding mechanism and affinity towards HST of three flavonoids: rutin, luteolin, and apigenin by different techniques: UV-Vis, fluorescence, fluorescence resonance energy transfer (FRET) combined with molecular docking. UV-Vis results indicate an interaction between flavonoids and HST. It was observed that HST fluorescence was quenched by these three flavonoids via a static process. All the interactions were moderate and the main driving forces are hydrophobic (ΔH > 0 and ΔS > 0) for rutin and luteolin binding or electrostatic (ΔH < 0 and ΔS > 0) for apigenin binding. FRET and molecular docking studies confirm the fluorescence static quenching mechanism by flavonoid binding. The binding of all three flavonoids increases HST stability. These results present the potential use of HST in target-oriented delivery of flavonoids and possibly other drugs into cells.