Inhibition of Glutamate Carboxypeptidase by Phosphoryl and Thiophosphoryl Derivatives of Glutamic and 2-Hydroxyglutaric Acid

Abstract

Representative phosphoryl and thiophosphoryl derivatives of ( S )-glutamic or ( S )-2-hydroxyglutaric acid were synthesized and evaluated for their inhibitory potency against the glutamate carboxypeptidase, carboxypeptidase G (CPG). It was observed that the inhibition of CPG was highly sensitive to the individual phosphorus ligands. The most potent inhibitors were the dibasic phosphoryl and thiophosphoryl derivatives of glutamic acid and the monobasic thiophosporyl derivatives of 2-hydroxyglutaric acid.