Drug Latentiation by γ-Glutamyl Transpeptidase

Article abstract of DOI:10.1021/jm00351a003

The N-γ-glutamyl derivatives of L-thiazolidine-4-carboxylic acid, 4-aminobutyric acid, 1-aminocyclopentanecarboxylic acid, 2-aminophenol, and p-fluoro-L-phenylalanine (compounds 6, 8, 9, 10, and 12 respectively) were synthesized using the synthom phthaloylglutamic anhydride.Their relative rates of cleavage by the enzyme γ-glutamyl transpeptidase (γ-GT) were determined in order to evaluate the possibility for their selective release by this enzyme which is elevated in certain pathological conditions.Compounds 6, 8, and 9 were not readily solvolyzed by γ-GT, but compounds 10 and 12, as well as the N-γ-glutamylated derivatives of 3- and 4-aminophenol, were readily cleaved.