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Glutamine analogs

Antifolate Drugs or Glutamine Analogs Block Purine Nucleotide Biosynthesis... [Pg.293]

Several reactions of IMP biosynthesis require folate derivatives and glutamine. Consequently, antifolate drugs and glutamine analogs inhibit purine biosynthesis. [Pg.301]

Novogrodosky, A., Nehring, RE., Jr and Meister, A. (1979). Inhibition of amine acid transport into lymphoid cells by the glutamine analog L-2-amino-4-oxo-5-chloropentanoate. Proc. Natl Acad. Sci. USA 76, 4932-4935. [Pg.123]

L Moroder, W Gohring, P Lucietto, J Musiol, R Schaarf, P Thamm, G Bovermann, G Wiinsch, J Lundberg, G Tatemoto. Synthesis of porcine intestinal peptide PHI and its 24-glutamine analog, (aminolysis without base). Hoppe Seyler s Z Physiol Chem 364, 1563, 1983. [Pg.235]

In the presence of an excess of the glutamine analog, DON, the enzyme is readily inactivated irreversibly (7). This substance behaves as an active-site-directed alkylating agent in a number of enzymes which utilize glutamine as substrate (3). With the use of 6-I4C-DON, the amount of inhibitor covalently bound to protein can be directly measured and, as shown in Fig. 1, this amount is linearly correlated with the extent of inhibition of catalytic activity. The simplest explanation of this behavior is that irreversible reaction of one molecule of DON with the enzyme inactivates one catalytic site, probably by combination with an essential group at that site. With this assumption the concentration of active sites in an enzyme preparation may be calculated for the... [Pg.85]

Several steps in the de novo purine biosynthetic pathway may be inhibited by antitumor agents. Steps requiring glutamine (2 and 5) are sensitive to azaserine, a glutamine analog. Its structure is shown in Figure 10.7. Steps requir-... [Pg.271]

Figure 10.7 Structure of azaserine, a glutamine analog and inhibitor of purine biosynthesis. Figure 10.7 Structure of azaserine, a glutamine analog and inhibitor of purine biosynthesis.
GlutaDON is a combination therapy for the treatment of cancer consisting of PEGylated glutaminase, which breaks down the glutamine and the glutamine analog 6-diazo-5-oxo-L-norleucine (DON). [Pg.1990]

The glutamine analogs discussed above are toxic substances and should be treated accordingly. Azaserine has been reported to be an active mutagen in bacterial systems [D. S. Longnecker, T. J. Curphey, S. T. James, D. 8. Daniel, and N. J. Jacobs, Cancer Res. 34, 1658 (1974)1. [Pg.418]

As with other active site-directed irreversible inhibitors that form a reversible complex prior to covalent attachment, glutamine analogs normally exhibit saturation kinetics. The Ki for inactivation of the glutamine binding site may be calculated from a plot of inactivation half-time (T1/2) against the reciprocal inhibitor concentration or from competitive inhibition data. ... [Pg.422]

T. C. French, I. B. Dawid, and J. B. Buchanan, J. Biol. Chem. 238, 2186 (1963). " In some cases a cysteine has been identified indirectly by loss of a titratable sulfhydryl group after reaction with the glutamine analog. [Pg.423]

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). [Pg.26]

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. [Pg.81]


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See also in sourсe #XX -- [ Pg.233 , Pg.241 ]




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