Drug latentiation by gamma-glutamyl transpeptidase.

The N-gamma-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 synthon phthaloylglutamic anhydride. Their relative rates of cleavage by the enzyme gamma-glutamyl transpeptidase (gamma-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 gamma-GT, but compounds 10 and 12, as well as the N-gamma-glutamylated derivatives of 3- and 4-aminophenol, were readily cleaved.