Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.17.21 (
prostate-specific membrane antigen
)
1,761
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Glutamate carboxypeptidase II
(
GCPII
) is a membrane-bound cell surface peptidase. There is significant interest in the inhibition of
GCPII
as a means of neuroprotection, while
GCPII
inhibition as a method to treat prostate cancer remains a topic of further investigation. The key zinc-binding functional group of the well-characterized classes of
GCPII
inhibitors (phosphonates and phosphoramidates) is tetrahedral and negatively charged at neutral pH, while glutamyl urea class of inhibitors possesses a planar and neutral zinc-binding group. This study explores a new class of
GCPII
inhibitors, glutamyl sulfamides, which possess a putative net neutral tetrahedral zinc-binding motif. A small library containing six sulfamides was prepared and evaluated for inhibitory potency against purified
GCPII
in an enzymatic assay. While most inhibitors have potencies in the micromolar range, one showed promising sub-micromolar potency, with the optimal inhibitor in this series being aspartyl-glutamyl
sulfamide
(2d). Lastly, computational docking was used to develop a tentative binding model on how the most potent inhibitors interact with the ligand-binding site of
GCPII
.
...
PMID:Rationally designed sulfamides as glutamate carboxypeptidase II inhibitors. 2377 97
