The synthesis and biological activities of some aza analogs of amino acids. I. 4-Azaleucine, an inhibitory analog of leucine

Amino Acid Antagonist Death in Escherichia coli

“…Several of the amino acid antagonists studied have been reported to be incorporated into protein of E. coli: azatryptophan (10), 0-methylthreonine (17), azetidine carboxylic acid (5), and thiazolidine carboxylic acid (18). The leucine antagonists, methallylglycine (3) and azaleucine (16), have been shown to inhibit growth, but their incorporation into protein has not been demonstrated. To determine whether the incorporation of the antagonist into protein was a requisite for lethality, protein synthesis was inhibited with chloramphenicol (1).…”

The C3-N Bond Cleavage of 2-Amino-3-(N-substituted-amino)-propionic Acids Catalyzed byl-Methionine γ-Lyase

“…14 ) DL-2-Amino-3-(N-methylamino)propionic acid, DL-2-amino-3-(N-hydroxyethylamino)propionic acid, and DL-2-amino-3-(N-acetamino)propionic acid were synthesized from 2-acetaminoacrylic acid, and methylamine, ethanolamine and acetamide, respectively, as follows. 2-Acetaminoacrylic acid (1.5 g, 11 mmol) and amines (75 mmol) were dissolved in water (10 ml).…”

Transport of L-4-azaleucine in Escherichia coli

“…DL-4-Azaleucine was first synthesized in 1963 as an analogue of leucine (24) and subsequently isolated as a metabolic product of Streptomyces neocaliberis (5). It is a potent growth inhibitor of Escherichia coli (20,24), Salmonella typhimurium (25), Pseudomonas mildenbergii (5), Proteus rettgeri (5), Sarcina lutea (5), Leuconostoc dextranicum (5), and blue-green algae (1).…”

“…DL-4-Azaleucine was first synthesized in 1963 as an analogue of leucine (24) and subsequently isolated as a metabolic product of Streptomyces neocaliberis (5). It is a potent growth inhibitor of Escherichia coli (20,24), Salmonella typhimurium (25), Pseudomonas mildenbergii (5), Proteus rettgeri (5), Sarcina lutea (5), Leuconostoc dextranicum (5), and blue-green algae (1). The toxicity of azaleucine has been associated with its incorporation into protein in place of leucine, resulting in inactive enzymes (4,20), and with its repression of the biosynthetic enzymes for leucine, isoleucine, and valine (6,20,28).…”

“…The toxicity of azaleucine has been associated with its incorporation into protein in place of leucine, resulting in inactive enzymes (4,20), and with its repression of the biosynthetic enzymes for leucine, isoleucine, and valine (6,20,28). In E. coli, L-leucine prevents the inhibition of growth by azaleucine, whereas isoleucine or valine fails to prevent inhibition (24). Of the 20 naturally occurring amino acids tested for reversal of the growth inhibition caused by azaleucine in S. typhimurium (25), only leucine completely reversed the inhibition.…”