Small molecules designed to specifically activate or inactivate protein functions have been useful to study biological processes. PROTACS are small molecule chimera which comprise a ligand and a peptide recognition motif for an E3 ligase. These novel reagents exploit the ubiquitin-mediated proteasome degradation pathway to target the ligand-bound protein for intracellular degradation. Here, we report that an estrogen receptor (ER)-targeting PROTACS that causes degradation of ER is able to potently inhibit endothelial cell differentiation in a three-dimensional angiogenic sprouting assay. These findings support the use of ER-targeting PROTACS as probes of angiogenesis.
|Number of pages||4|
|Journal||Bioorganic and Medicinal Chemistry Letters|
|State||Published - Jun 2 2005|
Bibliographical noteFunding Information:
We are grateful to the Department of Ophthalmology and Visual Sciences (University of Kentucky) for generous start-up funds to R.M. and the Kentucky Lung Cancer Research Program for financial support to K.K.
- Endothelial cell differentiation
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry