Interaction of daunomycin antibiotic with human α1-acid glycoprotein: Spectroscopy and modeling

Abstract Daunomycin (DM) is a clinically used antitumor anthracycline antibiotic. Understanding the interaction of DM with plasma proteins such as human α 1 -acid glycoprotein (AGP) is essential to understanding their pharmacokinetics and pharmacodynamics. The interaction between DM and AGP was investigated using fluorescence quenching technique, circular dichroism (CD) spectroscopy and molecular modeling methods. The binding constants of DM with AGP were determined at different temperatures based on the fluorescence quenching results. In addition, the thermodynamic functions standard enthalpy (Δ H ) and standard entropy (Δ S ) for the binding reaction were calculated to be −14.23 kJ mol −1 and 37.80 J mol −1  K −1 , according to the van't Hoff equation, which indicated that hydrophobic, hydrogen bond, electrostatic interactions are important driving forces for protein-DM association. Furthermore, the spectra data suggested that the association between DM and AGP did not change molecular conformation of AGP and a docking model of DM and AGP around Trp160 provided further details of the binding site topology.