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Using the Protein Chip to Screen Agonists and Antagonists of the Androgen Receptor

Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College

^* To whom correspondence should be addressed. E-mail: dugh{at}imm.ac.cn.

	Abstract

Based on its important physical and pathological function, the androgen receptor (AR) is regarded as a significant drug target. In this report, the authors describe a novel strategy of protein chip technology to screen agonists and antagonists of AR. First, the AR ligand binding domain (AR-LBD) was expressed in Escherichia coli, purified, and then immobilized on a silane-polysaccharide surface of a protein chip. Second, the affinities of methyltestosterone (MT) and fluorescent-labeled testosterone for the AR-LBD protein chip were determined. Third, a converse strategy of the protein chip was tested to evaluate its reliability as a drug screening method. Fourth, a 10,067-compound library was screened to find new ligands of AR. From the results, the K_d of testosterone and the IC₅₀ of MT are consistent with the literature (0.61 vs. 0.49 nM 2.88 vs. 3.90 nM, respectively). The Z' factor of the high-throughput screening (HTS) method was 0.76, which meets the requirement of drug screening (>0.4). Finally, 3 active ligands of AR were identified with their IC₅₀ values of 3.63, 2.19, and 1.71 µM, respectively. In summary, the novel strategy of the AR-LBD protein chip was suitable for HTS at the molecular level. (Journal of Biomolecular Screening XXXX:xx-xx)

First published on March 18, 2008, doi:10.1177/1087057108315881

Journal of Biomolecular Screening 2008;13:276.

A more recent version of this article appeared on April 1, 2008


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