Differential presentation of protein interaction surfaces on the androgen receptor defines the pharmacological actions of bound ligands.

Journal Article

The pharmacological activity of different nuclear receptor ligands is reflected by their impact on receptor structure. Thus, we asked whether differential presentation of protein-protein interaction surfaces on the androgen receptor (AR), a surrogate assay of receptor conformation, could be used in a prospective manner to define the pharmacological activity of bound ligands. To this end, we identified over 150 proteins/polypeptides whose ability to interact with AR is influenced in a differential manner by ligand binding. The most discriminatory of these protein-AR interactions were used to develop a robust compound-profiling tool that enabled the separation of ligands into functionally distinguishable classes. Importantly, the ligands within each class exhibited similar pharmacological activities, a result that highlights the relationship between receptor structure and activity and provides direction for the discovery of novel AR modulators.

Full Text

Duke Authors

Cited Authors

  • Norris, JD; Joseph, JD; Sherk, AB; Juzumiene, D; Turnbull, PS; Rafferty, SW; Cui, H; Anderson, E; Fan, D; Dye, DA; Deng, X; Kazmin, D; Chang, C-Y; Willson, TM; McDonnell, DP

Published Date

  • April 24, 2009

Published In

Volume / Issue

  • 16 / 4

Start / End Page

  • 452 - 460

PubMed ID

  • 19389631

Electronic International Standard Serial Number (EISSN)

  • 1879-1301

Digital Object Identifier (DOI)

  • 10.1016/j.chembiol.2009.01.016

Language

  • eng

Conference Location

  • United States