DON = 6-Diazo-5-oxo-L norleucine

Kisner DL, Catane R, Muggia FM. The rediscovery of DON (6-diazo-5-oxo-L-norleucine). Recent results. Cancer Res 74 258-263, 1980. 

Nitrogen can be transferred from glutamine into many other substrates.102 Several antibiotic analogs of glutamine have been useful in studying these processes. Examples are the streptomyces antibiotics L-azaserine and 6-diazo-5-oxo-L-norleucine (DON). 

A series of anti-metabolites have also been prepared which contain an alkylating moiety to enable the antagonists to inhibit the appropriate enzyme irreversibly, by formation of a co-valent bond94. Two compounds of this type to have had a clinical trial are the glutamine antagonists azaserine 44 and 6-diazo-5-oxo-L-norleucine (DON 45). 

Approaches to the syntheses of the Streptomyces anticancer antibiotics 6-diazo-5-oxo-L-norleucine (73 DON) and azotomycin... 

Azaserine (O-diazoacetyl-L-serine) and 6-diazo-5-oxo-L-norleucine (DON) and L-2-amino-3-ureidoproprionic acid (albizziine) are inhibitors of a wide range of glutamine using enzymes in which the amide-amino group is transferred. 

In several studies of the L-glutamine D-fructose 6-phosphate amidotransferase reaction it has been shown that specific glutamine antagonists may be used to inhibit the reaction. Ghosh et al. (1960) showed that 6-diazo-5-oxo-L-norleucine (DON) was a potent inhibitor of the enzyme, whereas azaserine was less effective. The glutamine analogs, methionine sulfoxide and y-glutamyl hydrazide, on the other hand, were not inhibitory (Clarke and Pasternak, 1962). 

The glutamine analog 6-diazo-5-oxo-L-norleucine (DON) inhibits L-glu-tamine n-fructose-6-phosphate amidotransferase (Section III) in the-pathway of conversion of C-glucose to both sialic acid and N-acetylga-lactosamine and, as expected, thereby inhibits incorporation of C-glu-cose into OSM. With glucose as the sole carbohydrate source in the incubation medium, DON also inhibits incorporation of radioactive amino acids into OSM but causes a concomitant increased incorporation of labeled amino acid into other protein fractions these latter proteins may contain nonglycosylated polypeptide precursors of OSM. All the inhibitory effects of DON are prevented if glucosamine is present in the incul ition medium. 

DON, see 6-Diazo-5-oxo-norleucine DONV, see 5-Diazo-4-oxo-L-norvaline Drugs, see aho specific substances binding to receptor, 574 opiate, see Opiate receptors Dye-ligand conjugate, 563 Dyes, 00... 

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