title: Optical biosensor analysis in studying new synthesized bicalutamide analogs binding to androgen receptor.
abstract: Bicalutamide (Casodex®) is a non-steroidal anti-androgen drug used in the treatment of prostate cancer, which represents the second most common malignancy diagnosed in men worldwide. In this work, we analyze the ability of some novel bicalutamide analogs to bind the androgen receptor, by using an optical biosensor. Androgen receptor was covalently immobilized on a carboxy methyl dextran matrix. The immobilized receptor chip was then used for the binding experiments of the bicalutamide analogs. The (R)-bicalutamide dissociation constant was in good agreement to the value reported in literature obtained by using radiolabeled targets. Most of the new synthesized compounds showed higher androgen receptor binding level, when compared to the reference. Our results clearly indicate that the surface plasmon resonance (SPR) technique offers many advantages with respect to other available technologies in terms of studying biomolecular interactions. Moreover, this study provides an effective methodology for determining the binding affinity of novel chemical entities for the isolated androgen receptor, thus excluding possible off-target interactions occurring in conventional cell-based techniques.
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Fortugno
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: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Geneva, Switzerland.
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Carrupt
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 / Q000737:chemistry / Q000378:metabolism*; D015374:Biosensing Techniques / Q000379:methods*; D009570:Nitriles / Q000737:chemistry / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*; D020349:Surface Plasmon Resonance / Q000379:methods*; D014105:Tosyl Compounds / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000813:Anilides; D009570:Nitriles; D011944:Receptors, Androgen; D014105:Tosyl Compounds; C053541:bicalutamide
keywords: Androgen receptor; Bicalutamide analogs; Optical biosensor; Protein binding; Surface plasmon resonance