Affinity of miriplatin to human serum albumin and its effect on protein structure and stability

Abstract

In this report, circular dichroism (CD) along with steady-state fluorescence spectroscopy and molecular modeling investigations were carried out to better understand the interaction of miriplatin with human serum albumin (HSA). The presence of miriplatin in solution is found to destabilize the native structure of HSA: The tertiary structure of HSA was changed and the microenvironment of Trp residue became more hydrophobic; the binding affinity of HSA with miriplatin indicating by 8-Anilino-1-naphthalenesulfonic acid (ANS) fluorescence study was 1.74ÿ106L/mol; miriplatin induced the denaturation and unfolding of HSA and disrupted the polar contacts and decreasing the reversibility of the unfolding process of protein. In addition, molecular modeling studies indicated miriplatin bound to domain II of HSA by hydrophobic force, hydrogen bonds, and electrostatic force interactions. HSA retained most of its esterase activity even after its binding with miriplatin. These results provide valuable insight into the binding mechanism between miriplatin and a plasma protein that is known to play an important role in the drug delivery of medicinal drugs to target organs.