title: Comparative study on the interaction of two binuclear Pt (II) complexes with human serum albumin: Spectroscopic and docking simulation assessments.
abstract: Human serum albumin (HSA) principally tasks as a transport carrier for a vast variety of natural compounds and pharmaceutical drugs. In the present study, two structurally related binuclear Pt (II) complexes containing cis, cis-[Me2Pt (μ-NN) (μ-dppm) PtMe2] (1), and cis, cis-[Me2Pt(μ-NN)(μ dppm) Pt((CH2)4)] (2) in which NN=phthalazine and dppm=bis (diphenylphosphino) methane were used to investigate their interaction with HSA, using UV-Vis absorption spectroscopy, fluorescence, circular dichroism and molecular dynamic analyses. The spectroscopic results suggest that upon binding to HSA, the binuclear Pt (II) complexes could effectively induce structural alteration of this protein. These complexes can bind to HSA with the binding affinities of the following order: complex 2>complex 1. Moreover, the thermodynamic parameters of binding between these complexes and HSA suggested the existence of entropy-driven spontaneous interaction, which mostly dominated with the hydrophobic forces. The ANS fluorescence results also indicated that two binuclear Pt (II) complexes were competing for the binding to the hydrophobic regions on HSA. In addition, competitive displacement assay and docking simulation study revealed that complexes 1 and 2 bind to the drug binding sites II and I on HSA, respectively. Furthermore, complex 2, with the higher binding affinity for HSA, shows more denaturing effect on this protein. Considering the protein structural damages in the pathway of harmful side effects of platinum drugs, complex 1 with the moderate binding affinity and low denaturing effect might be of high significance.
authors.affiliation: Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran; Department of Biological Science and Biotechnology, Faculty of Science, University of Kurdistan, Sanandaj, Iran.
authors.forename: Mohammad Bagher
authors.initials: MB
authors.lastname: Shahsavani
authors.affiliation: Department of Biological Science and Biotechnology, Faculty of Science, University of Kurdistan, Sanandaj, Iran.
authors.forename: Shamseddin
authors.initials: S
authors.lastname: Ahmadi
authors.affiliation: Department of Chemistry, College of Sciences, Shiraz University, Shiraz, Iran.
authors.forename: Marzieh Dadkhah
authors.initials: MD
authors.lastname: Aseman
authors.affiliation: Department of Chemistry, College of Sciences, Shiraz University, Shiraz, Iran.
authors.forename: S Masoud
authors.initials: SM
authors.lastname: Nabavizadeh
authors.affiliation: Department of Chemistry, Shiraz University of Technology, Shiraz, Iran.
authors.forename: Mohammad Mehdi
authors.initials: MM
authors.lastname: Alavianmehr
authors.affiliation: Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran. Electronic address: ryousefi@shirazu.ac.ir.
authors.forename: Reza
authors.initials: R
authors.lastname: Yousefi
mesh_terms: D002942:Circular Dichroism; D006801:Humans; D010984:Platinum / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics
chemical_list: D012709:Serum Albumin; D010984:Platinum
keywords: Binuclear Pt (II) complexes; Circular dichroism; Fluorescence study; Human serum albumin