title: Species-dependent binding of new synthesized bicalutamide analogues to albumin by optical biosensor analysis.
abstract: The binding of some novel bicalutamide analogues to human serum albumin (HSA) and rat serum albumin (RSA) was investigated by surface plasmon resonance (SPR) based optical biosensor technique. The serum protein binding of the bicalutamide analogues was determined and compared to that of the parent compound. Furthermore, HSA and RSA were used as target plasma proteins, in order to highlight possible differences among species when performing pharmacokinetic studies. HSA and RSA were covalently immobilized on carboxymethyl dextran matrixes, using an amine coupling procedure. The anchoring method was validated by determining the dissociation constant (KD) of a standard analyte to confirm that the binding properties of the proteins were maintained. The ranking of the bicalutamide analogues for their HSA and RSA bound fractions was used to compare the behaviour of the two albumins. Most of the bicalutamide analogues showed higher binding levels with respect to the lead compound, (R)-bicalutamide. Further, meaningful differences in the binding level to the two serum proteins were obtained. The dissociation constants (KD) of the interaction between the lead compound, (R)-bicalutamide, and the two proteins were calculated. As a result, the KD obtained with HSA was one order of magnitude higher than that obtained with RSA. The observed differences in the HSA and RSA bonding of the bicalutamide analogues increase the knowledge on the possible low reliability in extrapolating the distribution data obtained on animals to humans. This work demonstrates that SPR based optical biosensor technique is well suited for the medium-high throughput screening of compounds' ligand binding to serum albumins.
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Fortugno
authors.affiliation: Department of Pharmaceutical Sciences, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands.
authors.forename: Toon
authors.initials: T
authors.lastname: van der Gronde
authors.affiliation: Institute of Organic Synthesis and Photoreactivity, National Research Council, Bologna, Italy.
authors.forename: Greta
authors.initials: G
authors.lastname: Varchi
authors.affiliation: Institute of Organic Synthesis and Photoreactivity, National Research Council, Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Guerrini
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy. Electronic address: carlo.bertucci@unibo.it.
authors.forename: Carlo
authors.initials: C
authors.lastname: Bertucci
mesh_terms: D000813:Anilides / Q000378:metabolism*; D000818:Animals; D015374:Biosensing Techniques / Q000379:methods; D001798:Blood Proteins / Q000378:metabolism; D003911:Dextrans / Q000378:metabolism; D006801:Humans; D007854:Lead / Q000378:metabolism; D009570:Nitriles / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D015203:Reproducibility of Results; D012709:Serum Albumin / Q000378:metabolism*; D020349:Surface Plasmon Resonance / Q000379:methods; D014105:Tosyl Compounds / Q000378:metabolism*
chemical_list: D000813:Anilides; D001798:Blood Proteins; D003911:Dextrans; D009570:Nitriles; D012709:Serum Albumin; D014105:Tosyl Compounds; D007854:Lead; C014392:carboxymethyl dextran; C053541:bicalutamide
keywords: Bicalutamide analogues; Human serum albumin; Optical biosensor; Protein binding; Rat serum albumin