Inhibition of L asparagine synthetase by a new amino acid antibiotic with antitumor activity: L (αS,5S) α amino 3 chloro 4,5 dihydro 5 isoxazoleacetic acid (NSC-163501)

D. A. Cooney, H. N. Jayaram, J. A. Ryan, V. H. Bono

27 Scopus citations


NSC 163501 and its hydroxy analog (αS,4S,5R) α amino 3 chloro 4 hydroxy 4,5 dihydro 5 isoxazoleacetic acid (NSC 176324) are powerful inhibitors of the utilization of L glutamine by L asparagine synthetase both in vitro and in vivo. The type of inhibition produced in vitro is concluded to be apparently competitive on the basis of graphic analysis. L glutamine in large molar excess effectively antagonizes inhibition produced by these agents; however, established inhibition is concluded to be irreversible on the basis of dialysis experiments. Attempts to demonstrate alteration of the inhibitor molecule in the act of catalysis were unsuccessful.

Original languageEnglish (US)
Pages (from-to)793-802
Number of pages10
Issue number6
StatePublished - Jan 1 1974


ASJC Scopus subject areas

  • Medicine(all)

Cite this