Design of highly potent urea-based, exosite-binding inhibitors selective for glutamate carboxypeptidase II
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Glutamate Carboxypeptidase II antagonists & inhibitors chemistry metabolism MeSH
- HEK293 Cells drug effects MeSH
- Enzyme Inhibitors chemistry metabolism pharmacology MeSH
- Protein Conformation MeSH
- Humans MeSH
- Urea chemistry MeSH
- Molecular Structure MeSH
- Drug Evaluation, Preclinical methods MeSH
- Drug Design MeSH
- Chemistry Techniques, Synthetic MeSH
- Binding Sites MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Glutamate Carboxypeptidase II MeSH
- Enzyme Inhibitors MeSH
- Urea MeSH
We present here a structure-aided design of inhibitors targeting the active site as well as exosites of glutamate carboxypeptidase II (GCPII), a prostate cancer marker, preparing potent and selective inhibitors that are more than 1000-fold more active toward GCPII than its closest human homologue, glutamate carboxypeptidase III (GCPIII). Additionally, we demonstrate that the prepared inhibitor conjugate can be used for sensitive and selective imaging of GCPII in mammalian cells.
References provided by Crossref.org
Uncovering the essential roles of glutamate carboxypeptidase 2 orthologs in Caenorhabditis elegans
PDB
4X3R
