Discovery of Cyclic Peptide Estrogens and Antiestrogens
Abstract
The identification of proteins involved in the initiation of disease and the identification of small molecules that modulate these proteins are of great importance for the discovery of improved therapeutics. For example, compounds that potentiate estrogen receptor-mediated gene expression comprise a large class of currently employed drugs. These compounds can both treat breast cancer and provide hormone replacement therapy. Although initially beneficial, over time current clinically prescribed compounds can exhibit deleterious side-effects that include the development of drug resistance and an increased risk of breast cancer. We initially hypothesized that a recently described genetic system termed split-intein mediated circular ligation of peptides and proteins (SICLOPPS) (PNAS, 1999, 96, 13638- 13643) could enable the identification of small cyclic peptides that exhibit estrogenic and antiestrogenic activity in recombinant yeast systems. However, preliminary data suggests that SICLOPPS does not function or express well in yeast. Current efforts are directed at using related systems to investigate oncogenic protein tyrosine kinases and to identify proteins involved in estrogen-responsive pathways. These studies may identify new drug targets involved in the proliferation of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2004
- Accession Number
- ADA424093
Entities
People
- Daniel D. Clark
Organizations
- Pennsylvania State University