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.
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.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002455:Cell Division; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000032:analysis; D004926:Escherichia coli / Q000201:enzymology; D005974:Glutamate-Ammonia Ligase / Q000037:antagonists & inhibitors; D005972:Glutaminase / Q000037:antagonists & inhibitors; D005973:Glutamine / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007555:Isoxazoles / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000032:analysis / Q000473:pathology; D008099:Liver / Q000201:enzymology; D051379:Mice; D010080:Oxazoles / Q000494:pharmacology*; D051381:Rats; D013302:Streptomyces / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; D007555:Isoxazoles; D010080:Oxazoles; D005973:Glutamine; D005972:Glutaminase; D005974:Glutamate-Ammonia Ligase; C006303:acivicin; D005998:Glycine