The influence of L-norvalyl-N3-4-methoxyfumaroyl-L-2,3-diaminopropanoic acid, an antifungal agent, on mammalian cells in tissue culture.
Murine leukemia L1210 cells contain active glucosamine 6-phosphate synthase inhibited by N3-4-methoxyfumaroyl-L-2,3-diaminopropanoic acid (FMDP). However, FMDP-peptides do not exhibit any cytotoxicity against these cells, HeLa S3 human cervical carcinoma cells, and LL2 murine Lewis lung carcinoma cells. It is suggested that the lack of cytotoxicity of FMDP-peptides, in spite of good drug uptake and the presence of target enzyme might be due to the poor rate of peptides cleavage by the intracellular peptidases.
Bontemps-Gracz
M
M
Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdańsk, Poland.
Milewski
S
S
Borowski
E
E
D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D004151:Dipeptides / Q000494:pharmacology*; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000037:antagonists & inhibitors; D006801:Humans; D007930:Leucine / Q000378:metabolism; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014529:Uridine / Q000378:metabolism
D004151:Dipeptides; D009842:Oligopeptides; C068215:norvalyl-N(3)-(4-methoxyfumaroyl)-2,3-diaminopropionic acid; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing); D007930:Leucine; D013936:Thymidine; D014529:Uridine