Peptide antagonists of the human estrogen receptor

Estrogen receptor a transcriptional activity is regulated by distinct confo rmational states that are the result of ligand binding. Phage display was u sed to identify peptides that interact specifically with either estradiol- or tamoxifen-activated estrogen receptor alpha. When these peptides were co expressed with estrogen receptor alpha in cells, they functioned as ligand- specific antagonists, indicating that estradiol-agonist and tamoxifen-parti al agonist activities do not occur by the same mechanism. The ability to re gulate estrogen receptor a transcriptional activity by targeting sites outs ide of the ligand-binding pocket has implications for the development of es trogen receptor a antagonists for the treatment of tamoxifen-refractory bre ast cancers.