Various fluorinated analogues of folic acid and methotrexate have been synthesized from fluorine-containing glutamic acids, ornithine, and dipeptides. These analogues were evaluated as substrates or inhibitors of three folate-dependent enzymes, folylpoly-γ-glutamate synthetase (FPGS), γ-glutamyl hydrolase (γ-GH) and dihydrofolate reductase (DHFR), and also for their effects on intact mammalian cells; e.g., transport and cytotoxicity. The most marked effects of fluorine substitution were observed with FPGS and γ-GH which catalyze the ligation or hydrolysis of glutamyl moieties, respectively.
|Original language||English (US)|
|Number of pages||12|
|Journal||ACS Symposium Series|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Chemical Engineering(all)