Development of peptide antagonists for the androgen receptor using combinatorial peptide phage display.

Journal Article (Journal Article)

Under the auspices of the Nuclear Receptor Signaling Atlas (NURSA), we have undertaken to evaluate the feasibility of targeting nuclear receptor-coactivator surfaces for new drug discovery. The underlying objective of this approach is to provide the research community with reagents that can be used to modulate the transcriptional activity of nuclear receptors. Using combinatorial peptide phage display, we have been able to develop peptide antagonists that target specific nuclear receptor (NR)-coactivator binding surfaces. It can be appreciated that reagents of this nature will be of use in the study of orphan nuclear receptors for whom classical ligands have not yet been identified. In addition, because the interaction of coactivators with the receptor is an obligate step for NR transcriptional activity, it is anticipated that peptides that block these interactions will enable the definition of the biological and pharmacological significance of individual NR-coactivator interactions. In this report, we describe the use of this approach to develop antagonists of the androgen receptor by targeting its coactivator-binding pocket and their use to study the coactivator-binding surface of this receptor. Based on our findings, we believe that molecules that function by disrupting the androgen receptor-cofactor interactions will have use in the treatment of prostate cancer.

Full Text

Duke Authors

Cited Authors

  • Chang, C-Y; Abdo, J; Hartney, T; McDonnell, DP

Published Date

  • October 2005

Published In

Volume / Issue

  • 19 / 10

Start / End Page

  • 2478 - 2490

PubMed ID

  • 16051662

International Standard Serial Number (ISSN)

  • 0888-8809

Digital Object Identifier (DOI)

  • 10.1210/me.2005-0072


  • eng

Conference Location

  • United States