Fortugno Cecilia, Varchi Greta, Guerrini Andrea, Carrupt Pierre-Alain, Bertucci Carlo
Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy.
Institute of Organic Synthesis and Photoreactivity, National Research Council, Bologna, Italy.
J Pharm Biomed Anal. 2014 Jul;95:151-7. doi: 10.1016/j.jpba.2014.03.002. Epub 2014 Mar 12.
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.
比卡鲁胺（康士得®）是一种用于治疗前列腺癌的非甾体类抗雄激素药物，前列腺癌是全球男性中第二常见的诊断出的恶性肿瘤。在这项工作中，我们通过使用光学生物传感器分析了一些新型比卡鲁胺类似物与雄激素受体结合的能力。雄激素受体被共价固定在羧甲基葡聚糖基质上。然后将固定化的受体芯片用于比卡鲁胺类似物的结合实验。（R）-比卡鲁胺的解离常数与通过使用放射性标记靶标获得的文献报道值吻合良好。与参比物相比，大多数新合成的化合物显示出更高的雄激素受体结合水平。我们的结果清楚地表明，在研究生物分子相互作用方面，表面等离子体共振（SPR）技术相对于其他现有技术具有许多优势。此外，本研究提供了一种有效的方法来确定新型化学实体与分离的雄激素受体的结合亲和力，从而排除了传统基于细胞的技术中可能发生的脱靶相互作用。
