title: Surface plasmon resonance assay of inhibition by pharmaceuticals for thyroxine hormone binging to transport proteins.
abstract: We developed a surface plasmon resonance (SPR) assay to estimate the competitive inhibition by pharmaceuticals for thyroxine (T4) binding to thyroid hormone transport proteins, transthyretin (TTR) and thyroxine binding globulin (TBG). In this SPR assay, the competitive inhibition of pharmaceuticals for introducing T4 into immobilized TTR or TBG on the sensor chip can be estimated using a running buffer containing pharmaceuticals. The SPR assay showed reproducible immobilization of TTR and TBG, and the kinetic binding parameters of T4 to TTR or TBG were estimated. The equilibrium dissociation constants of TTR or TBG measured by SPR did not clearly differ from data reported for other binding assays. To estimate the competitive inhibition of tetraiodothyroacetic acid, diclofenac, genistein, ibuprofen, carbamazepine, and furosemide, reported to be competitive or noncompetitive pharmaceuticals for T4 binding to TTR or TBG, their 50% inhibition concentrations (IC50) (or 80% inhibition concentration, IC80) were calculated from the change of T4 responses in sensorgrams obtained with various concentrations of the pharmaceuticals. Our SPR method should be a useful tool for predicting the potential of thyroid toxicity of pharmaceuticals by evaluating the competitive inhibition of T4 binding to thyroid hormone binding proteins, TTR and TBG.
authors.affiliation: Pharmaceutical Research Division, Shionogi & Co., Toyonaka, Osaka 561-0825, Japan; Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-8558, Japan. Electronic address: hiroki.kinouchi@shionogi.co.jp.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kinouchi
authors.affiliation: Pharmaceutical Research Division, Shionogi & Co., Toyonaka, Osaka 561-0825, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Matsuyama
authors.affiliation: Department of Biochemistry, Kobe Pharmaceutical University, Higashinada-ku, Kobe 658-8558, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitagawa
authors.affiliation: Pharmaceutical Research Division, Shionogi & Co., Toyonaka, Osaka 561-0825, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kamimori
mesh_terms: D001667:Binding, Competitive; D004008:Diclofenac / Q000737:chemistry / Q000378:metabolism; D020128:Inhibitory Concentration 50; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D011228:Prealbumin / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D020349:Surface Plasmon Resonance; D013974:Thyroxine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*; D056825:Thyroxine-Binding Globulin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004364:Pharmaceutical Preparations; D011228:Prealbumin; D056825:Thyroxine-Binding Globulin; D004008:Diclofenac; C011126:tetraiodothyroacetic acid; D013974:Thyroxine
keywords: Surface plasmon resonance; Thyroid hormone; Thyroid hormone transport proteins