SYNTHESIS OF N-[N-(4-DEOXY-4-AMINO-10-METHYLPTEROYL)-4-FLUOROGLUTAMYL]-GAMMA-GLUTAMATE, AN UNUSUAL SUBSTRATE FOR FOLYLPOLY-GAMMA-GLUTAMATE SYNTHETASE AND GAMMA-GLUTAMYL HYDROLASE

N-[N-(4-Deoxy-4-amino-10-methylpteroyl)-4-fluoroglutamyl]-γ-glutamate has been synthesized and its ability to serve as a substrate for folylpolyglutamate synthetase and γ-glutamyl hydrolase has been investigated. It was anticipated that this compound would be a substrate for both of these enzymes. Although the title compound proved to be a good substrate for folylpolyglutamate synthetase, hydrolysis catalyzed by γ-glutamyl hydrolase was unexpectedly slow. These results suggest the use of fluoroglutamate-containing peptides as hydrolase-resistant folates or antifols in a variety of chemotherapeutic regimens. © 1990, American Chemical Society. All rights reserved.