4-N-hydroxy-L-2,4-diaminobutyric acid. A strong inhibitor of glutamine synthetase

S Fushiya; K Maeda; T Funayama; S Nozoe

doi:10.1021/jm00397a037

4-N-hydroxy-L-2,4-diaminobutyric acid. A strong inhibitor of glutamine synthetase

J Med Chem. 1988 Feb;31(2):480-3. doi: 10.1021/jm00397a037.

Authors

S Fushiya¹, K Maeda, T Funayama, S Nozoe

Affiliation

¹ Pharmaceutical Institute, Tohoku University, Sendai, Japan.

PMID: 2892937
DOI: 10.1021/jm00397a037

Abstract

Analogues of glutamic acid were synthesized and evaluated for their inhibitory activity toward glutamine synthetase (EC 6.3.1.2; GS). The title compound, 4-N-hydroxy-L-2,4-diaminobutyric acid (NH-DABA), showed a potent inhibitory activity against GS from both sheep brain and soybean. The inhibition is competitive with respect to glutamic acid and the Ki values of sheep brain GS and soybean GS for NH-DABA are 0.007 mmol and 0.021 mmol, respectively. The activity of inhibition is comparable to those of L-methionine sulfoximine and 2-amino-4-(hydroxymethyl-phosphinyl)butyric acid (phosphinothricin).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aminobutyrates / chemical synthesis
Aminobutyrates / pharmacology*
Animals
Glutamate-Ammonia Ligase / antagonists & inhibitors*
Sheep
Structure-Activity Relationship

Substances

Aminobutyrates
4-N-hydroxy-2,4-diaminobutyric acid
Glutamate-Ammonia Ligase