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

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.