title: Interaction of cisplatin with human serum albumin. Drug binding mode and protein secondary structure.
abstract: Cis-diamminedichloroplatinum(II) (cisplatin) is an antitumor drug, which forms intrastrand cross-links DNA adducts. Protein interaction with cisplatin-DNA complexes induces DNA bending and biopolymer structural changes. This study is designed to examined the interaction of cisplatin with human serum albumin (HSA) in aqueous solution at physiological pH with drug concentrations of 0.0001 mM to 0.1 mM, and HSA (fatty acid free) concentration of 2% w/v. Absorption spectra and Fourier transform infrared (FTIR) spectroscopy with its self-deconvolution and second derivative resolution enhancement, as well as curve-fitting procedures, were used to determine the drug binding mode, drug binding constant and the protein secondary structure in aqueous solution. Spectroscopic evidence showed that at low drug concentration (0.0001 mM), minor cisplatin-protein interaction occurs, while at higher drug content (0.001 mM), major Pt-HSA complexation takes place via protein C=O, C-N and S-H donor groups with overall binding constant K = 8.52 x 10(2) M-1. At high drug concentration, cisplatin binding results in major protein secondary structural changes from that of the alpha-helix 55% (free HSA) to 45% and beta-sheet 22% (free HSA) to 32%, in the cisplatin-HSA complexes. The observed spectral changes indicate a partial unfolding of the protein structure, in the presence of cisplatin at high drug concentrations.
authors.affiliation: Department of Chemistry-Biology, University of Québec at Trois-Rivières, Canada.
authors.forename: J F
authors.initials: JF
authors.lastname: Neault
authors.forename: H A
authors.initials: HA
authors.lastname: Tajmir-Riahi
mesh_terms: D001665:Binding Sites; D002945:Cisplatin / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D017433:Protein Structure, Secondary; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D019265:Spectroscopy, Near-Infrared
chemical_list: D012709:Serum Albumin; D002945:Cisplatin