1. L-[alphaS, 5S]-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (NSC-163501): a new amino acid antibiotic with the properties of an antagonist of L-glutamine.
- Author
-
Jayaram HN, Cooney DA, Ryan JA, Neil G, Dion RL, and Bono VH
- Subjects
- Animals, Cell Division, Cells, Cultured, DNA, Neoplasm analysis, Escherichia coli enzymology, Glutamate-Ammonia Ligase antagonists & inhibitors, Glutaminase antagonists & inhibitors, Glutamine metabolism, Glutamine pharmacology, Glycine pharmacology, Leukemia L1210 analysis, Leukemia L1210 pathology, Liver enzymology, Mice, Rats, Streptomyces metabolism, Antibiotics, Antineoplastic pharmacology, Glutamine antagonists & inhibitors, Glycine analogs & derivatives, Isoxazoles pharmacology, Oxazoles pharmacology
- Abstract
L-[alphaS,5S]-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (NSC-163501), an antibiotic elaborated by Streptomyces sviceus, has been shown to be a powerful inhibitor of many mammalian and bacterial reactions involving the transfer of nitrogen from the gamma-carboxamide of L-glutamine. Thus, the utilization of L-glutamine for the synthesis of carbamyl phosphate, L-asparagine, guanosine-5'-monophosphate, cytidine-5'-triphosphate, N-formylglycinamidine ribonucleotide, NAD, glucosamine-6-phosphate, and anthranilic acid is strongly or totally inhibited by a concentration of NSC-163501 of 1 X 10(-3) M. L-Glutamate synthetase of Escherichia coli is only modestly inhibited and 5-phosphoribosylamine synthesis in fetal rat liver is comparatively refractory to inhibition. NSC-163501 treatment of L1210 cells growing in a low L-glutamine culture medium produced arrest in G or early S phase. Of the amino acids tested, only L-glutamine antagonized such growth inhibition.
- Published
- 1975