Skip to main content

Glutamine Antagonists

  • Chapter

Abstract

This chapter deals primarily with compounds whose biological activity may be ascribed to interference with functions of glutamine. Some consideration is also given to molecules that decrease the cellular pools of glutamine either by preventing its synthesis or by metabolically altering it once it is formed.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   74.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Aaronson, S.: Mode of action of azaserine on Gaffkya homari. J. Bact. 77, 548–551 (1959).

    PubMed  CAS  Google Scholar 

  • Abrams, R., Bentley, M.: Biosynthesis of nucleic acid purines. III. Guanosine 5′-phosphate formation from xanthosine 5′-phosphate and L-glutamine. Arch. Biochem. Biophys. 79, 91–110 (1959).

    Article  CAS  Google Scholar 

  • Alexandre, G. P. J., Morelle, J., Haxhe, J. J., Michelsen, P., Ypersele, C. V., Michaux, M., Kestens, P.: Considerations a propos de quatre cas d’homogreffes renales. Acta Chirurgica Belgica 68, 367–385 (1964).

    Google Scholar 

  • Alexandre, G. P. J., Murray, J. E., Dammin, G. J., Nolan, B.: Immunosuppressive drug therapy in canine renal and skin homografts. Transplantation 1, 432–461 (1963).

    Article  PubMed  CAS  Google Scholar 

  • Anderson, E. P., Brockman, R. W.: Biochemical effects of duazomycin A in the mouse plasma cell neoplasm 70429. Biochem. Pharmacol. 12, 1335–1354 (1963).

    Article  PubMed  CAS  Google Scholar 

  • Anderson, E. P., Jacquez, J. A.: Azaserine resistance in a plasma-cell neoplasm without change in active transport of the inhibitor. Cancer Res. 22, 27–37 (1962).

    PubMed  CAS  Google Scholar 

  • Ansfield, F. J.: Phase I study of azotomycin (NSC-56654). Cancer Chemother. Rep. 46, 37–40 (1965).

    PubMed  CAS  Google Scholar 

  • Ayengar, P., Roberts, E.: Inhibition of the utilization of glutamine by Lactobacillus arabinosus. Growth 17, 201–214 (1953).

    PubMed  CAS  Google Scholar 

  • Baker,B-R.: Design of active-site directed irreversible enzyme inhibitors. New York: John Wiley and Sons 1967.

    Google Scholar 

  • Barclay, R. K., Garfinkel, E., Phtlltpps, M. A.: Effects of 6-diazo-5-oxo-L-norleucine on the incorporation of precursors into nucleic acids. Cancer Res. 22, 809–814 (1962).

    CAS  Google Scholar 

  • Barclay, R. K., Phillipps, M. A.: Effects of 6-diazo-5-oxo-L-norleucine and other tumor inhibitors on the biosynthesis of nicotinamide adenine dinucleotide in mice. Cancer Res. 26, 282–286 (1966).

    PubMed  CAS  Google Scholar 

  • Barg,W., Boggiano,E., Sloan,N., De Renzo,E.C.: Inhibitors of de novo formylglycinamide ribotide synthesis in pigeon liver extracts. Fed. Proc. 16, 150 (1957).

    Google Scholar 

  • Barker,S. A., Bassham,J. A., Calvin, M., Quarck, U. C.: Sites of azaserine inhibition during photosynthesis by scenedesmus. J. Amer. chem. Soc. 78, 4632–4635 (1956).

    Article  CAS  Google Scholar 

  • Bartz, Q. R., Elder,C. C., Frohardt, R. P., Fusari, S. A., Haskell, T. H., Johannessen, D. W., Ryder, A.: Isolation and characterization of azaserine. Nature (Lond.) 173, 72–73 (1954).

    Article  CAS  Google Scholar 

  • Bennett, L. L., Jr., Schabel, F. M., Jr., Skipper, H. E.: Studies on the mode of action of azaserine. Arch. Biochem. Biophys. 64, 423–436 (1956).

    Article  PubMed  CAS  Google Scholar 

  • Bennett, L. L., Jr., Smithers, D.: Feedback inhibition of purine biosynthesis in H. Ep. 2 cells by adenine analogs. Biochem. Pharmacol. 13, 1331–1339 (1964).

    Article  PubMed  CAS  Google Scholar 

  • Blattner, R. J., Williamson, A. P., Simonsen, L.: Teratogenic changes in early chick embryos following administration of antitumor agent (azaserine). Proc. Soc. exp. Biol. (N.Y.) 97, 560–564 (1958).

    CAS  Google Scholar 

  • Bonasera, N., Mangione, G., Bonavita, V.: Diphosphopyridine nucleotide synthesis in brain following injection of various compounds. Biochem. Pharmacol. 12, 633–636 (1963).

    Article  PubMed  CAS  Google Scholar 

  • Borek, E., Miller, H. K., Sheiness, P., Waelsch, H.: The effect of the sulfoxide from DL- methionine on glutamic acid and glutamine metabolism. J. biol. Chem. 163, 347 (1946).

    CAS  Google Scholar 

  • Brock, T. D., Brock, M. L.: Reversal of azaserine by phenylalanine. J. Bact. 81, 212–217 (1961).

    PubMed  CAS  Google Scholar 

  • Brockman, R. W., Anderson, E. P.: Biochemistry of cancer (metabolic aspects). Ann. Rev. Biochem. 82, 463–512 (1963).

    Article  Google Scholar 

  • Brockman, R. W., Chtjmley, S.: Inhibition of formylglycinamide ribonucleotide synthesis in neoplastic cells by purines and analogs. Biochim. biophys. Acta (Amst.) 95, 365–379 (1965).

    CAS  Google Scholar 

  • Brockman, R. W., Pittillo, R. F., Shaddix, S., Hill, D. L.: Mode of action of azotomycin. Antimicrobial Agents and Chemotherapy 1969, 56–62 (1970).

    Google Scholar 

  • Bruce, W. R., Meeker, B. E., Valeriote, F. A.: Comparison of the sensitivity of normal hematopoietic and transplanted lymphoma colony-forming cells to chemotherapeutic agents administered in vivo. J. nat. Cancer Inst. 37, 233–245 (1966).

    PubMed  CAS  Google Scholar 

  • Carter, S. K.: Azotomycin (NSC-56654)-clinical brochure. Cancer Chemother. Rep. 1, part 3, 207–217 (1968).

    Google Scholar 

  • Chakraborty, K. P., Hurlbert, R. B.: Role of glutamine in the biosynthesis of cytidine nucleotides in Escherichia coli. Biochim. biophys. Acta (Amst.) 47, 607–609 (1961).

    Article  CAS  Google Scholar 

  • Clarke, D. A., Reilly, H. C., Stock, C. C.: A comparative study of 6-diazo-5-oxo-L-norleucine and O-diazocetyl-L-serine on Sarcoma 180. Antibiot. and Chemother. 7, 653–671 (1957).

    CAS  Google Scholar 

  • Coggin, J. H., Jr., Martin, W. R.: 6-Diazo-5-oxo-L-norleucine inhibition of Escherichia coli. J. Bact. 89, 1348–1353 (1965).

    PubMed  CAS  Google Scholar 

  • Colsky, J., Shnider, B. I., Franzino, A., Perez, J.: Observations in patients with metastatic malignancy treated with duazomycin A. Clin. Pharmacol, and Ther. 7, 352–358 (1966).

    CAS  Google Scholar 

  • Cooney, D. A., Handschtjmacher, R. E.: L-Asparaginase andL-asparagine metabolism. Ann. Rev. Pharmacol. 10, 421–440 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Cramer,G. T., Sartorelli, A. C.: Studies on the mechanism of the azaserine-induced decrease in the activity of thymidine kinase. Biochem. Pharmacol. 18, 1355–1362 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Curry, J., Greenberg, J.: Filament formation in radioresistant mutants of Escherichia coli S after treatment with ultraviolet light and radiomimetic agents. J. Bact. 83, 38–42 (1962).

    PubMed  CAS  Google Scholar 

  • Dagg,C. P., Karnofsky, D. A.: Teratogenic effects of azaserine on the chick embryo. J. exp. Zool. 130, 555–572 (1955).

    Google Scholar 

  • Dawid, I. B., French, T. C., Buchanan, J. M.: Azaserine-reactive sulfhydryl group of 2-form- amido-iV-ribosylacetamide 5’-phosphate: L-glutamine amidoligase (adenosine diphosphate) II. Degradation of azaserine-C-14-labeled enzyme. J. biol. Chem. 238, 2178–2185 (1963).

    PubMed  CAS  Google Scholar 

  • Delhumeau-Arrecillas, G., Burris, R. H.: Effects of azaserine on Azotobacter agilis. J. Bact. 78, 740–741 (1959).

    PubMed  CAS  Google Scholar 

  • De Robertis, E., Sellinger, O. Z., De L. Arnaiz, G. R., Alberici, M., Zieher, L. M.: Nerve endings in methionine sulphoximine convulsant rats, a neurochemical and ultrastructural study. J. Neurochem. 14, 81–89 (1967).

    Article  PubMed  Google Scholar 

  • Devoe, S. E., Rigler, N. E., Shay, A. J., Martin, J. H., Boyd, T. C., Backus, E. J., Mowat, J.H., Bohonos, N.: Alazopeptin: production, isolation and chemical characteristics. Antibiot. Ann. 1956–1957, 730–735 (1957).

    Google Scholar 

  • Dewald, H. A., Moore, A. M.: 6-Diazo-5-oxo-L-norleucine, a new tumor-inhibitory substance. Preparation of L (D and L)-forms. Amer. chem. Soc. 129th Meeting Abstr. 13–14 M (1956).

    Google Scholar 

  • Dion, H. W., Fusari, S. A., Jakubowski, Z. L., Zora, J. G., Bartz,Q. R.: 6-Diazo-5-oxo-L- norleucine, a new tumor-inhibitory substance. II. Isolation and characterization. J. Amer, chem. Soc. 78, 3075–3077 (1956).

    Article  CAS  Google Scholar 

  • Duvall, L. R.: New agent data summaries: azaserine. Cancer Chemother. Rep. 7, 65–86 (1960a).

    Google Scholar 

  • Duvall, L. R.: New agent data summaries: 6-diazo-5-oxo-L-norleucine. Cancer Chemother. Rep. 7, 86–98 (1960b).

    Google Scholar 

  • Eagle, H., Oyama, V. I., Levy, M., Horton, C. L., Fleischman, R.: The growth response of mammalian cells in tissue culture to L-glutamine and L-glutamic acid. J. biol. Chem. 218, 607–616 (1956).

    PubMed  CAS  Google Scholar 

  • Edelson, J., Skinner,C. G., Shive, W.: Synthesis and biological activity of some -(substituted) glutamines. J. med. pharm. Chem. 1, 165–170 (1959).

    Article  PubMed  CAS  Google Scholar 

  • Eidinoff, M. L., Knoll, J. E., Marano, B., Cheong, L.: Pyrimidine studies. I. Effect of DON (6-diazo-5-oxo-L-norleucine) on incorporation of precursors into nucleic acid pyrimidines. Cancer Res. 18, 105–109 (1958).

    CAS  Google Scholar 

  • El-Asmar, F. A., Greenberg, D. M.: Studies on the mechanism of inhibition of tumor growth by the enzyme glutaminase. Cancer Res. 26, 116–122 (1966).

    PubMed  CAS  Google Scholar 

  • Elliott, H. W., Gale, E. F.: Glutamine-synthesizing system of Staphylococcus aureus: its inhibition by crystal violet and methionine sulfoxide. Nature (Lond.) 161, 129–130 (1948).

    Article  CAS  Google Scholar 

  • Ellison, R. R., Karnofsky, D. A., Sternberg, S. S., Murphy, M. L., Burchenal, J. H.: Clinical trials of O-diazoacetyl-L-serine (azaserine) in neoplastic disease. Cancer (Philad.) 7, 801–814(1954).

    Google Scholar 

  • Folbergrova, J.: The effect of methionine sulphoximine on the protein metabolism of brain cortex slices. J. Neurochem. 10, 775–782 (1963).

    Article  PubMed  CAS  Google Scholar 

  • Foley, H. T., Shnider, B. I., Gold, G. L., Rius, J.: A pilot study of methotrexate, duazomycin A, and radiation therapy in carcinoma of the lung. J. new Drugs 6, 105–110 (1966).

    PubMed  CAS  Google Scholar 

  • Foucher, G., Wuyts, J. L., Mack, G., Geisert, J., Fontaine, J. L.: Influence du traitement combiné azasérine/imuran sur la survie de Tallotransplant renal primaire chez le chien. Compt. Rend. Séances Soc. Biol. (Paris) 161, 1404–1406 (1967).

    CAS  Google Scholar 

  • French, T. C., Dawid, I. B., Day, R A., Buchanan, J. M.: Azaserine-reactive sulfhydryl group of 2-formamido-iV-ribosylacetamide 5’-phosphate: L-glutamine amidoligase (adenosine diphosphate). I. The purification and properties of the enzyme from Salmonella typhimurium and the synthesis of L-azaserine-C14. J. biol. Chem. 288, 2171–2177 (1963).

    Google Scholar 

  • Fby, B. A.: Glutamine synthesis by Micrococcus pyogenes var. aureus. Biochem. J. 59, 579–589 (1955).

    Google Scholar 

  • Ftjsari, S. A., Frohardt, R. P., Ryder, A., Haskell, T. H., Johannessen, D.W., Elder, C.C., Bartz, Q. R.: Azaserine, a new tumor-inhibitory substance. Isolation and characterization. J. Amer. chem. Soc. 76, 2878–2881 (1954a).

    Article  Google Scholar 

  • Fusari, S. A., Haskell, T. H., Frohardt, R. P., Bartz, Q. R.: Azaserine, a new tumor-inhibitory substance. Structural studies. J. Amer. chem. Soc. 76, 2881–2883 (1954b).

    Article  CAS  Google Scholar 

  • Gershenovich, Z. S., Krichevskaya, A. A., Kolousek, J.: The effect of raised oxygen pressure and of methionine sulphoximine on the glutamine synthetase activity of rat brain. J. Neurochem. 10, 79–82 (1963).

    Article  PubMed  CAS  Google Scholar 

  • Ghosh, S., Blumenthal, H. J., Davidson, E., Roseman, S.: Glucosamine metabolism. V. Enzymatic synthesis of glucosamine 6-phosphate. J. biol. Chem. 235, 1265–1273 (1960).

    PubMed  CAS  Google Scholar 

  • Gibson, F., Pittard, J., Reich, E.: Ammonium ions as the source of nitrogen for tryptophan biosynthesis in whole cells of Escherichia coli. Biochim. biophys. Acta (Amst.) 186, 573–576 (1967).

    Google Scholar 

  • Gmelin, R., Strauss, G., Hassenmaier, G.: Isolierung von 2 neuen pflanzlichen Aminosäuren: S (β-carboxyäthyl)-L-cystein und Albizziin aus den Samen von Albizzia julibrissin Durazz. (Mimosaceae). Z. Naturforsch. 13 B, 252–256 (1958).

    Google Scholar 

  • Goldin, A., Humphreys, S. R., Venditti, J. M., Mantel, N.: Factors influencing antitumor synergism: relation to screening methodology. Ann. N. Y. Acad. Sci. 76, 932–938 (1958).

    Article  PubMed  CAS  Google Scholar 

  • Goldthwait, D. A.: 5-Phosphoribosylamine, a precursor of glycinamide ribotide. J. biol. Chem. 222, 1051–1068 (1956).

    PubMed  CAS  Google Scholar 

  • Gots, J. S., Bird, T. J., Mudd, S.: L-Azaserine as an inducing agent for the development of phage in the lysogenic Escherichia coli, K-12. Biochim. biophys. Acta (Amst.) 17, 449–450 (1955).

    Article  CAS  Google Scholar 

  • Gots, J. S., Gollub, E. G.: Purine metabolism in bacteria. IV. L-Azaserine as an inhibitor. J. Bact. 72, 858–864 (1956).

    PubMed  CAS  Google Scholar 

  • Greenberg, D. M., Blumenthal, G., Ramadan, M. A.: Effect of administration of the enzyme glutaminase on the growth of cancer cells. Cancer Res. 24, 957–963 (1964).

    PubMed  CAS  Google Scholar 

  • Greenberg, J., Mandell, J. D., Woody, P. L.: A preliminary report-resistance and cross- resistance of Escherichia coli mutants to radiomimetic agents. Cancer Chemother. Rep. 11, 51–56 (1961).

    PubMed  CAS  Google Scholar 

  • Greenlees, J., Lepage, G. A.: Purine biosynthesis and inhibitors in ascites cell tumors. Cancer Res. 16, 808–813 (1956).

    PubMed  CAS  Google Scholar 

  • Hagemann, G., Penasse, L., Teillon, J.: Sur un dérivé de la sérine, la O-carbamyl-D-sérine, produit par un streptomyces. Biochim. biophys. Acta (Amst.) 17, 240–243 (1955).

    Article  CAS  Google Scholar 

  • Hager, S. E., Jones, M. E.: Initial steps in pyrimidine synthesis in Ehrlich ascites carcinoma in vitro. I. Factors affecting the incorporation of 14C-bicarbonate into carbon 2 of the uracil ring of the acid-soluble nucleotides of intact cells. J. biol. Chem. 240, 4556–4563 (1965).

    Google Scholar 

  • Halvorson, H.: Some effects of azaserine on yeast metabolism. Antibiot. and Chemother. 4, 948–961 (1954).

    CAS  Google Scholar 

  • Hansen, H. J., Vandevoorde, J. P., Bennett, K. J., Giles, W. G.: Azaserine and thiopurines: I. I. hibition of S-180 mouse tumor and antibody synthesis. J. lab. clin. Med. 63, 801–818 (1964).

    PubMed  CAS  Google Scholar 

  • Hartman, S.C.: The interaction of 6-diazo-5-oxo-L-norleucine with phosphoribosyl pyrophosphate amidotransferase. J. biol. Chem. 238, 3036–3047 (1963).

    PubMed  CAS  Google Scholar 

  • Hartman, S. C.: Purines and pyrimidines. In: Greenberg, D. M. (Ed.): Metabolic pathways, Vol. IV, pp. 1–68. 3 rded. New York: Academic Press 1970.

    Google Scholar 

  • Hartman, S. C., Levenberg, B., Buchanan, J. M.: Biosynthesis of the purines. XI. Structure, enzymatic synthesis, and metabolism of glycinamide ribotide and (α-JV-formyl)-glycinamide ribotide. J. biol. Chem. 221, 1057–1070 (1956).

    PubMed  CAS  Google Scholar 

  • Haskell, C. M., Canellos, G. P.: Asparagine biosynthesis in KB tumor cells: inhibitor studies with asparagine and glutamine antagonists. Cancer Res. 30, 1081–1083 (1970).

    PubMed  CAS  Google Scholar 

  • Hayes, D. M., Costa, J., Moon, J. H., Hoogstraten, B., Harley, J. B.: Combination therapy with thioguanine (NSC 752) and azaserine (NSC 742) for multiple myeloma. Cancer Chemother. Rep. 51, 235–238 (1967).

    PubMed  CAS  Google Scholar 

  • Haxhe, J. J., Alexandre, G. P. J., Kestens, P. J.: The effect of imuran and azaserine on liver function tests in the dog. Arch. int. Pharmacodyn. 168, 366–372 (1967).

    PubMed  CAS  Google Scholar 

  • Heathcote, J. G., Pace, J.: Inhibition of the growth of Leuconostoc mesenteroides by the toxic factor from “agenized” zein: reversal by L-glutamine. Nature (Lond.) 166, 353–354 (1950).

    Article  CAS  Google Scholar 

  • Hedegaard, J., Maspero-Segre, S., Thoai, N.-V., Rocjhe, J.: Influence de l’histidine et de ses métabolites sur la biosynthèse des purines par Escherichia coli B. IV. Action sur des cultures inhibées par l’azasérine. Comp. Rend. Seances Soc. Biol. (Paris) 153, 767–771 (1959a).

    CAS  Google Scholar 

  • Hedegaard, J., Maspero-Segre, S., Thoai, N.-V., Roche, J.: Influence de l’histidine et de ses métabolites sur la biosynthèse des purines par Escherichia coli B. V. Mode d’action dans des cultures inhibées par l’azasérine. Comp. Rend. Seances Soc. Biol. (Paris) 153, 954–959 (1959b).

    CAS  Google Scholar 

  • Held, I., Wells, W., Koenig, H.: Metabolic effects of azaserine in rat brain. J. Neurochem. 16, 537–542 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Hemmerly, J., Demerec, M.: Tests of chemicals for mutagenecity. Cancer Res., Suppl. 3, 69–75 (1955).

    Google Scholar 

  • Henderson, J. F.: Feedback inhibition of purine biosynthesis in ascites tumor cells. J. biol. Chem. 237, 2631–2635 (1962).

    PubMed  CAS  Google Scholar 

  • Henderson, J. F.: Feedback inhibition of purine biosynthesis in ascites tumor cells by purine analogs. Biochem. Pharmacol. 12, 551–556 (1963).

    Article  PubMed  CAS  Google Scholar 

  • Henderson, J. F., Junga, I. G.: Inhibition of ascites tumor growth by 4-aminopyrazolo(3,4-D) pyrimidine in combination with azaserine, 6-mercaptopurine, and thioguanine. Cancer Res. 20, 1618–1624 (1960).

    PubMed  CAS  Google Scholar 

  • Hersh, E. M.: Immunosuppression by L-glutaminase in vitro. Proc. Amer. Ass. Cancer Res. 12, 39 (1971).

    Google Scholar 

  • Hersh, E. M., Brown, B. W.: Inhibition of immune response by glutamine antagonism: effect of azotomycin on lymphocyte blastogenesis. Cancer Res. 31, 834–840 (1971).

    PubMed  CAS  Google Scholar 

  • Heyn, R. M., Brubaker, C. A., Burchenal, J. H., Cramblett, H. G., Wolff, J. A.: The comparison of 6-mercaptopurine with the combination of 6-mercaptopurine and azaserine in the treatment of acute leukemia in children: results of a cooperative study. Blood 15, 350–359 (1960).

    PubMed  CAS  Google Scholar 

  • Hurlbert, R. B., Kämmen, H. O.: Formation of cytidine nucleotides from uridine nucleotides by soluble mammalian enzymes: requirements for glutamine and guanosine nucleotides. J. biol. Chem. 235, 443–449 (1960).

    CAS  Google Scholar 

  • Iyer, V. N., Szybalski, W.: The mechanism of chemical mutagenesis. I. Kinetic studies on the action of triethylene melamine (TEM) and azaserine. Proc. nat. Acad. Sei. (Wash.) 44, 446–456 (1958).

    Article  CAS  Google Scholar 

  • Iyer, V. N., Szybalski, W.: Mutagenic effect of azaserine in relation to azaserine resistance in Escherichia coli. Science 129, 839–840 (1959).

    Article  PubMed  CAS  Google Scholar 

  • Jacobs, S. P., Wodinsky, I., Kensler, C. J., Venditti, J.: Therapy of experimental leukemias with combinations of L-asparaginase and glutamine antagonists. Proc. Amer. Ass. Cancer Res. 10, 43 (1969).

    Google Scholar 

  • Jacquez, J. A.: Active transport of O-diazoacetyl-L-serine and 6-diazo-5-oxo-L-norleucine in Ehrlich ascites carcinoma. Cancer Res. 17, 890–896 (1957).

    PubMed  CAS  Google Scholar 

  • Jacquez, J. A.: Concentrative uptake of 6-diazo-5-oxo-L-norleucine by Sarcoma 180, liver and muscle in vivo. Proc. Soc. exp. Biol. (N. Y.) 99, 611–613 (1958).

    CAS  Google Scholar 

  • Jacquez, J. A.: Transport and exchange diffusion of L-tryptophan in Ehrlich cells. Amer. J. Physiol. 200, 1063–1068 (1961).

    PubMed  CAS  Google Scholar 

  • Jacquez, J. A., Sherman, J. H.: Enzymatic degradation of azaserine. Cancer Res. 22, 56–61 (1962).

    PubMed  Google Scholar 

  • Kämmen, H. O., Hurlbert, R. B.: The formation of cytidine nucleotides and RNA cytosine from orotic acid by the Novikoff tumor in vitro. Cancer Res. 19, 654–663 (1959).

    PubMed  Google Scholar 

  • Kandaswamy, T. S., Henderson, J. F.: Inhibition of ascites tumor growth by the trypanocide, ethidium bromide, in combination with azaserine. Nature (Lond.) 195, 85 (1962).

    Article  CAS  Google Scholar 

  • Kaplan, L. H., Reilly, H. C., Stock, C. C.: Action of azaserine on Escherichia coli. J. Bact. 78, 511–519 (1959).

    PubMed  CAS  Google Scholar 

  • Kaplan, S. R., Hayslett, J. P., Calabresi, P.: Treatment of advanced Wegener’s granulomatosis with azathioprine and duazomycin A. New Eng. J. Med. 278, 239–244 (1968).

    Article  CAS  Google Scholar 

  • Karnofsky, D. A., Bevelander, G.: Effects of DON (6-diazo-5-oxo-L-norleucine) and azaserine on the sand-dollar embryo. Proc. Soc. exp. Biol. (N. Y.) 97, 32–37 (1958).

    CAS  Google Scholar 

  • Karnofsky, D. A., Golbey, R. B., Li, M. C.: Remissions induced in trophoblastic tumors by 6-diazo-5-oxo-L-norleucine (DON). Proc. Amer. Ass. Cancer Res. 5, 33 (1964).

    Google Scholar 

  • Kilgore, W. W., Greenberg, J.: Filament formation and resistance to l-methyl-3-nitro-l- nitrosoguanidine and other radiomimetic compounds in Escherichia coli. J. Bact. 81, 258– 266 (1961).

    Google Scholar 

  • Kjaer, A., Larsen, P. O.: Amino acid studies. Part II. Structure and synthesis of Albizziine (L-2-amino-3-ureidopropionic acid), an amino acid from higher plants. Acta chem. Scand. 13, 1565–1574 (1959).

    Article  CAS  Google Scholar 

  • Klingman, J. D., Handler, P.: Partial purification and properties of renal glutaminase. J. biol. Chem. 232, 369–380 (1958).

    PubMed  CAS  Google Scholar 

  • Lamar, C., Jr.: The duration of the inhibition of glutamine synthetase by methionine sulfoximine. Biochem. Pharmacol. 17, 636–640 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Lamar, C., Jr., Sellinger, O. Z.: The inhibition in vivo of cerebral glutamine synthetase and glutamine transferase by the convulsant methionine sulfoximine. Biochem. Pharmacol. 14, 489–506 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Lee, K.-H., Yuzuriha, Y.: Studies on growth and cell division. III. Action of azaserine on cell division. J. pharm. Sci. 58, 290–293 (1964).

    Article  Google Scholar 

  • Lefkowitz, E. R., Creasey, W. A., Calabresi, P., Sartorelli, A. C.: Clinical and pharmacologic effects of combinations of 6-thioguanine and duazomycin A in patients with neoplastic disease. Cancer Res. 25, 1207–1212 (1965).

    PubMed  CAS  Google Scholar 

  • Legal, M.-L., Le Gal, Y., Roche, J., Hedegaard, J.: Purine biosynthesis: enzymatic formation of ribosylamine-5-phosphate from ribose-5-phosphate and ammonia. Biochem. biophys. Res. Commun. 27, 618–624 (1967).

    CAS  Google Scholar 

  • Lepage, G. A., Jones, M.: Purinethiols as feedback inhibitors of purine synthesis in ascites tumor cells. Cancer Res. 21, 642–649 (1961).

    PubMed  CAS  Google Scholar 

  • Levenberg, B., Melnick, I., Buchanan, J. M.: Biosynthesis of the purines. XV. The effect of aza-L-serine and 6-diazo-5-oxo-L-norleucine on inosinic acid biosynthesis de novo. J. biol. Chem. 225, 163–176 (1957).

    PubMed  CAS  Google Scholar 

  • Leventhal, B. G., Skeel, R. T., Yankee, R. A., Henderson, E. S.: L-Asparaginase (NSC 109229) plus azaserine (NSC 742) in acute lymphatic leukemia. Cancer Chemother. Rep. 54, 47–51 (1970).

    PubMed  CAS  Google Scholar 

  • Levintow, L.: The glutamyltransferase activity of normal and neoplastic tissues. J. nat. Cancer Inst. 15, 347–352 (1954).

    PubMed  CAS  Google Scholar 

  • Lingens, F., Lück, W., Müller, G.: Über die Wirkung von 5-oxo-6-diazo-norleuein und Albizziin auf die Biosynthese der Anthranilsäure in Saccharomyces cerevisiae. Hoppe-Seylers Z. physiol. Chem. 848, 282–289 (1966).

    Article  Google Scholar 

  • Livingston, R. B., Venditti, J. M., Cooney, D. A., Carter, S. K.: Glutamine analogs in chemotherapy. Advanc. Pharmacol, and Chemother. 8, 57–120 (1970).

    Article  CAS  Google Scholar 

  • Lowy, B., Williams, M. K.: The presence of a limited portion of the pathway de novo of purine nucleotide biosynthesis in the rabbit erythrocyte in vitro. J. biol. Chem. 235, 2924–2927 (1960).

    PubMed  CAS  Google Scholar 

  • Magill, G. B., Meyers, W. P. L., Reilly, H. C., Putnam, R. C., Magill, J. W., Sykes, M. P., Escher, G. C., Karnofsky, D. A., Btjrchenal, J. H.: Pharmacological and initial therapeutic observations on 6-diazo-5-oxo-L-norleucine (DON) in human neoplastic disease. Cancer (Philad.) 10, 1138–1150 (1957).

    Article  CAS  Google Scholar 

  • Mardashev, S. R., Kovalenko, N. A.: Effect of some glutamine analogs on glutaminase activity in rat kidney. Clostridium welchii SR-12 and Mycobacterium sp. n. Vop. med. Khim. 14, 319–323 (1968); Biol. Abstr. 51, 82403 (1970).

    Google Scholar 

  • Mashburn, L. T.: The effect of combined therapy with L-asparaginase on P1798 lymphosarcoma. Proc. Amer. Ass. Cancer Res. 9, 45 (1968).

    Google Scholar 

  • Maxwell, R. E., Nickel, V. S.: Filament formation in E. coli induced by azaserine and other antineoplastic agents. Science 120, 270–271 (1954).

    Article  PubMed  CAS  Google Scholar 

  • Maxwell, R. E., Nickel, V. S.: 6-Diazo-5-oxo-L-norleucine, a new tumor-inhibitory substance. V. Microbiologic studies of mode of action. Antibiot. and Chemother. 7, 81–89 (1957).

    CAS  Google Scholar 

  • Mccord, T. J., Skinner, C. G., Shive, W.: Some O-(substituted carbamyl) serines. J. org. Chem. 23, 1963–1965 (1958a).

    Article  CAS  Google Scholar 

  • Mccord, T. J., Ravel, J. M., Skinner, C. G., Shive, W.: O-Carbazyl-DL-serine, an inhibitory analog of glutamine. J. Amer. chem. Soc. 80, 3762–3764 (1958b).

    Article  CAS  Google Scholar 

  • Meister, A.: Biochemistry of the amino acids, Vols. I and II, 2nd ed. New York: Academic Press 1965.

    Google Scholar 

  • Mickelson, M. N., Flippin, R. S.: Effects of certain amino acid derivatives on microorganisms and Sarcoma 180. J. nat. Cancer Inst. 20, 495–512 (1958).

    PubMed  CAS  Google Scholar 

  • Miller, H. K., Balis, M. E.: Glutaminase activity of L-asparagine amidohydrolase. Biochem. Pharmacol. 18, 2225–2232 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Momparler, R. L., Jatfe, J. J.: Effect of azaserine on the incorporation of 14C-labeled purines and pyrimidines into the acid-soluble and nucleic acid fractions of Trypanosoma equiperdum. Biochem. Pharmacol. 14, 255–262 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Moore, E. C., Lepage, G. A.: In vivo sensitivity of normal and neoplastic mouse tissues to azaserine. Cancer Res. 17, 804–808 (1957).

    PubMed  CAS  Google Scholar 

  • Moore, J. A., Dice, J. R., Nicolaides, E. D., Westland, R. D., Whittle, E. L.: Azaserine, synthetic studies. I. J. Amer. chem. Soc. 76, 2884–2887 (1954).

    Article  CAS  Google Scholar 

  • Murphy, M. L., Karnofsky, D. A.: Effect of azaserine and other growth-inhibiting agents on fetal development of the rat. Cancer (Philad.) 9, 955–962 (1956).

    Article  CAS  Google Scholar 

  • Murray, J. E., Merrill, J. P., Harrison, J. H., Wilson, R. E., Dammin, G. J.: Prolonged survival of human kidney homografts by immunosuppressive drug therapy. New Eng. J. Med. 268, 1315–1323 (1963).

    Article  CAS  Google Scholar 

  • Murray, J. E., Sheil, A. G. R., Moseley, R., Knight, P., Mcgavic, J. D., Dammin, G. J.: Analysis of mechanism of immunosuppressive drugs in renal homotransplantation. Ann. Surg. 160, 449–473 (1969).

    Article  Google Scholar 

  • Murray, J. E., Wilson, R. E., Tilney, N. L., Merrill, J. R., Cooper, W. C., Birtch, A. G., Carpenter, C.B., Hager, E. B., Dammin, G. J., Harrison, J. H.: Five years experience in renal transplantation with immunosuppressive drugs: survival, function complications, and the role of lymphocyte depletion by thoracic duct fistula. Ann. Surg. 168, 416–435 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Nagano, H., Zalkin, H., Henderson, E. J.: The anthranilate synthetase-anthranilate-5- phosphoribosylpyrophosphate phosphoribosyl-transferase aggregate. J. biol. Chem. 245, 3810–3820 (1970).

    PubMed  CAS  Google Scholar 

  • Narkates, A. J., Pittillo, R. F.: Inhibition of nonproliferating Escherichia coli by azaserine. Antimicrobial Agents and Chemotherapy — 1963, 439–446 (1964).

    Google Scholar 

  • Narrod, S. A., Bonavita, V., Ehrenfeld, E. R., Kaplan, N. O.: Effect of azaserine on the biosynthesis of diphosphopyridine nucleotide in mouse. J. biol. Chem. 236, 931–935 (1961).

    PubMed  CAS  Google Scholar 

  • Narrod, S. A., Langan, T. A., Jr., Kaplan, N. O., Goldin, A.: Effect of azaserine (O-diazo- acetyl-L-serine) on the pyridine nucleotide levels of mouse liver. Nature (Lond.) 183, 1674 –1675 (1959).

    Google Scholar 

  • Neal, A. L., Libman, L., Smulson, M. E.: Influence of y-glutamyl-hydrazide on protein synthesis of Pseudomonas aeruginosa. Arch. Biochem. Biophys. 127, 426–428 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Neuman, R. E., Mccoy, T. A.: Dual requirement of Walker Carcinosarcoma 256 in vitro for asparagine and glutamine. Science 124, 124–125 (1956).

    Article  PubMed  CAS  Google Scholar 

  • Newell, G. W., Carman, W. W.: Effect of methionine on toxicity of crystalline “agene factor” against Leuconostoc mesenteroides. Fed. Proc. 9, 209 (1950).

    Google Scholar 

  • Nicolaides, E. D., Westland, R. D., Wittle, E. L.: Azaserine, synthetic studies. II. J. Amer. chem. Soc. 76, 2887–2891 (1954).

    Article  CAS  Google Scholar 

  • Okami, Y., Maeda, K., Kondo, H., Tanaka, T., Umezawa, H.: A streptomyces producing O- carbamyl-D-serine. J. Antibiot. (Tokyo) 15, 147–151 (1962).

    CAS  Google Scholar 

  • Oleson, J. J., Reith, A. R., Thie, R. S., Mjos, K. J., Calderella, L. A.: The comparative antitumor activity of the diazomycins. Fed. Proc. 19, 394 (1960).

    Google Scholar 

  • Pace, J., Mcdermott, E. E.: Methionine sulfoximine and some enzyme systems involving glutamine. Nature (Lond.) 169, 415–416 (1952).

    Article  CAS  Google Scholar 

  • Pasieka, A. E., Morgan, J. F.: Glutamine metabolism of normal and malignant cells cultivated in synthetic media. Nature (Lond.) 183, 1201–1202 (1959).

    Article  CAS  Google Scholar 

  • Patterson, M. K., Jr., Orr, G. R.: Asparagine biosynthesis by the Novikoff hepatoma. Isolation, purification, and mechanism studies of the enzyme system. J. biol. Chem. 243, 376–380 (1968).

    PubMed  CAS  Google Scholar 

  • Peters, E. L., Tower, D. B.: Glutamic acid and glutamine metabolism in cerebral cortex after seizures induced by methionine sulphoximine. J. Neurochem. 5, 80–90 (1959).

    Article  PubMed  CAS  Google Scholar 

  • Pine, E. K.: Concentrative uptake of azaserine by neoplastic plasma cells and lymphocytes. J. nat. Cancer Inst. 21, 973–984 (1958).

    PubMed  CAS  Google Scholar 

  • Pittillo, R. F.: Studies on the antimicrobial nature of action of azaserine. Antimicrobial Agents Annual 1960, 276–287 (1961).

    CAS  Google Scholar 

  • Pittillo, R. F., Hunt, D. E.: Azaserine and 6-diazo-5-oxo-L-norleucine (DON). In: Gottlieb, D., Shaw, P. D. (Eds.): Antibiotics, Vol. I, Mechanism of action, pp. 481–493. New York: Springer 1967.

    Google Scholar 

  • Pittillo, R. F., Narrates, A. J., Burns, J.: Comparison of the effects of some radiation modifiers on selected radiomimetic agents in microorganisms. Radiat. Res. 25, 401–409 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Pittillo, R. F., Quinnelly, B. G.: Further studies on the antimicrobial nature of action of azaserine. Antimicrobial Agents and Chemotherapy — 1961, 245–253 (1962).

    CAS  Google Scholar 

  • Preiss, J., Handler, P.: Biosynthesis of diphosphopyridine nucleotide. J. biol. Chem. 233, 493–500 (1958).

    PubMed  CAS  Google Scholar 

  • Price, K. E., Buck, R. E., Schlein, A., Siminoff, P.: A comparison of the in vitro susceptibility of HeLa and protozoan cells to antitumor antibiotics. Cancer Res. 22, 885–891 (1962).

    PubMed  CAS  Google Scholar 

  • Rabinovitz, M., Fisher, J. M.: S-Carbamylcysteine inhibition of protein synthesis by Ehrlich ascites tumor cells. J. nat. Cancer Inst. 28, 1165–1171 (1962).

    PubMed  CAS  Google Scholar 

  • Rabinovitz, M., Olson, M. E., Greenberg, D. M.: Role of glutamine in protein synthesis by the Ehrlich ascites carcinoma. J. biol. Chem. 222, 879–893 (1956).

    PubMed  CAS  Google Scholar 

  • Rabinovitz, M., Olson, M. E., Greenberg, D. M.: δ Hydroxylysine –an inhibitor of glutamine and protein synthesis by the Ehrlich ascites carcinoma cell. Cancer Res. 17, 885–889 (1957).

    PubMed  CAS  Google Scholar 

  • Rabinovitz, M., Olson, M. E., Greenberg, D. M.: Effect of glutamine analogs on amino acid incorporation into protein of some normal and neoplastic cells in vitro. Cancer Res. 19, 388–392 (1959).

    PubMed  CAS  Google Scholar 

  • Rao, K. V.: Chemistry of the duazomycins. I. Duazomycins A. Antimicrobial Agents and Chemotherapy — 1961, 178–183 (1962).

    CAS  Google Scholar 

  • Rao, K. V., Brooks, S. C., Ktjgelman, M., Romano, A. A.: Duazomycins A, B, and C, three antitumor substances. I. Isolation and characterization. Antibiotics Ann. 1959-60, 943–949 (1960).

    Google Scholar 

  • Ravel, J. M., Mccord, T. J., Skinner, C. G., Shive, W.: S-Carbamyl-L-cysteine, an inhibitory amino acid analogue. J. biol. Chem. 282, 159–168 (1958).

    Google Scholar 

  • Reilly, H. C.: Some aspects of azaserine, 6-diazo-5-oxo-L-norleucine, and β-2-thienylalanine. In: Wolstenholme, G. E. W., O’connor, C. M. (Eds.): Ciba Foundation Symposium: Amino acids and peptides with antimetabolic activity, pp. 62–74. Boston: Little, Brown and Co. 1958.

    Google Scholar 

  • Reitz, R. H., Slade, H. D., Netjhaus, F. C.: The biochemical mechanisms of resistance by Streptococci to the antibiotics D-cycloserine and O-carbamyl-D-serine. Biochemistry 6, 2561–2570 (1967).

    Article  PubMed  CAS  Google Scholar 

  • Roberts, E., Borges, P. R. F.: Patterns of free amino acids in growing and regressing tumors. Cancer Res. 15, 697–699 (1955).

    PubMed  CAS  Google Scholar 

  • Roberts, E., Frankel, S.: Free amino acids in normal and neoplastic tissues of mice as studied by paper chromatography. Cancer Res. 9, 645–648 (1949).

    PubMed  CAS  Google Scholar 

  • Roberts, J., Holcenberg, J. S., Dolowy, W. C.: Antineoplastic activity of highly purified bacterial glutaminases. Nature (Lond.) 227, 1136–1137 (1970).

    Article  CAS  Google Scholar 

  • Roberts, J., Holcenberg, J. S., Dolowy, W. C.: Physico-chemical and kinetic properties of an antitumor glutaminase and its crystallization. Proc. Amer. Ass. Cancer Res. 12, 13 (1971).

    Google Scholar 

  • Ronzio, R. A., Meister, A.: Phosphorylation of methionine sulfoximine by glutamine synthetase. Proc. nat. Acad. Sci. (Wash.) 59, 164–170 (1968).

    Article  CAS  Google Scholar 

  • Ronzio, R. A., Rowe, W. B., Meister, A.: Studies on the mechanism of inhibition of glutamine synthetase by methionine sulfoximine. Biochemistry 8, 1066–1075 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Roper, J. A., Mcilwain, H.: Preparation and antibacterial action of some compounds structurally related to glutamic acid. Their application in microbiological determination of small quantities of glutamine. Biochem. J. 42, 485–492 (1948).

    CAS  Google Scholar 

  • Rosenberg, S., Calabresi, P.: Enhanced suppression of the secondary immune response by combination of 6-mercaptopurine “duazomycin A.” Nature (Lond.) 199, 1101–1102 (1963).

    Article  CAS  Google Scholar 

  • Ross, D. L., Skinner, C. G., Shive, W.: S-(alkyl- and arylcarbamoyl)-L-cysteines. J. med. pharm. Chem. 3, 519–524 (1961).

    Article  PubMed  CAS  Google Scholar 

  • Roth, J. S., Wase, A., Reiner, L.: The distribution of S35-labeled L-methionine sulfoximine in the rat. Science 115, 236–238 (1952).

    Article  PubMed  CAS  Google Scholar 

  • Rowe, W. B., Ronzio, R. A., Meister, A.: Inhibition of glutamine synthetase by methionine sulfoximine. Studies on methionine sulfoximine phosphate. Biochemistry 8, 2674–2680 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Sartorelli, A. C., Booth, B. A.: Antineoplastic activity of combinations of 6-chloropurine and azaserine. Cancer Res. 20, 198–203 (1960).

    PubMed  CAS  Google Scholar 

  • Sartorelli, A. C., Booth, B. A.: Some factors affecting the tumor-inhibitory properties of combinations of azaserine and 6-chloropurine. Biochem. Pharmacol. 12, 847–853 (1963).

    Article  PubMed  CAS  Google Scholar 

  • Sartorelli, A. C., Booth, B. A.: Inhibition of the synthesis of thymine nucleotides by azaserine. Molec. Pharmacol. 8, 71–80 (1967).

    Google Scholar 

  • Sartorelli, A. C., Lepage, G. A.: Inhibition of ascites cell growth by combinations of 6- thioguanine and azaserine. Cancer Res. 18, 938–942 (1958a).

    PubMed  CAS  Google Scholar 

  • Sartorelli, A. C., Lepage, G. A.: Metabolic effects of 6-thioguanine. II. Biosynthesis of nucleic acid purines in vivo and in vitro. Cancer Res. 18, 1329–1335 (1958 b).

    Google Scholar 

  • Sartorelli, A. C., Schoolar, E. J., Jr., Krtjse, P. F., Jr.: Chemotherapy of Sarcoma 180 by combinations of DL-glyceraldehyde with 6-thioguanine or with azaserine and 6-chloropurine. Proc. Soc. exp. Biol. (N. Y.) 104, 266–268 (1960).

    CAS  Google Scholar 

  • Sartorelli,A. C., Upchtjrch, H. F., Bieber, A. L., Booth, B. A.: Some metabolic effects exerted by azaserine and purine analogs in vivo. Cancer Res. 24, 1202–1209 (1964).

    PubMed  CAS  Google Scholar 

  • Schabel, F. M., Jr., Skipper, H. E., Trader, M. W., Wilcox, W. S.: Experimental evaluation of potential anticancer agents. XIX. Sensitivity of nondividing leukemic cell populations to certain classes of drugs in vivo. Cancer Chemother. Rep. 48, 17–30 (1965).

    PubMed  CAS  Google Scholar 

  • Schroeder, D. D., Allison, A. J., Buchanan, J. M.: Biosynthesis of the purines. XXXII. Effect of Albizziin and other reagents on the activity of formylglycinamide ribonucleotide amidotransferase. J. biol. Chem. 244, 5856–5865 (1969).

    PubMed  CAS  Google Scholar 

  • Schroeder, J. M., Ansfield, F. J., Ctjrreri, A. R., Lepage, G. A.: Toxicity and clinical trial of azaserine and 6-thioguanine in advanced solid malignant neoplasms. Brit. J. Cancer 18, 449–458 (1964).

    Article  Google Scholar 

  • Schwartz, R. S. (Ed.): Proceedings of the symposium on immunosuppressive drugs. Fed. Proc. 26, 879–960 (1967).

    Google Scholar 

  • Sellinger, O. Z., Azctjrra, J. M., Ohlsson, W. G.: Methionine sulfoximine seizures. VIII. The dissociation of the convulsant and glutamine synthetase inhibitory effects. J. Pharmacol, exp. Ther. 164, 212–222 (1968).

    CAS  Google Scholar 

  • Sellinger, O. Z., Garaza, A.: The inhibition of cerebral glutamine synthetase by structural analogs of the convulsant DL-methionine sulfoximine. Biochem. Pharmacol. 15, 396–399 (1966).

    Article  PubMed  CAS  Google Scholar 

  • Sellinger, O. Z., Weiler, P., Jr.: The nature of the inhibition in vitro of cerebral glutamine synthetase by the convulsant, methionine sulfoximine. Biochem. Pharmacol. 12, 989–1000 (1963).

    Article  PubMed  CAS  Google Scholar 

  • Sheil, A. G. R., Dammin, G. J., Mitchell, R. M., Moseley, R. V., Murray, J. E.: The management, function, and histology of long functioning renal allografts in dogs on immunosuppressive drug therapy. Ann. Surg. 167, 467–485 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Sheil, A. G. R., Moseley, R. V., Murray, J. E.: Differential skin and renal homograft survival in dogs on immunosuppressive therapy. Surg. Forum 15, 166–168 (1964).

    PubMed  CAS  Google Scholar 

  • Shive, W., Skinner, C. G.: Amino acid analogs. In: Hochster, R. M., Quastel, J. H. (Eds.): Metabolic inhibitors, Vol. I, pp. 1–73. New York: Academic Press 1963.

    Google Scholar 

  • Short, L. N., Thompson, H. W.: Toxic factor from agenized proteins: infra-red measurements. J. chem. Soc. 1746–1749 (1951).

    Google Scholar 

  • Simard, R., Bernhard, W.: Le phénomène de la ségrégation nucléolaire: spécificité d’action de certains antimétabolites. Int. J. Cancer 1, 463–479 (1966).

    Article  PubMed  CAS  Google Scholar 

  • Skinner, C. G., McCord, T. J., Ravel, J. M., Shive, W.: O-Carbamyl-l-serine, an inhibitory analog of l-glutamine. J. Amer. chem. Soc. 78, 2412–2414 (1956).

    Google Scholar 

  • Skinner, C. G., Mckenna, G. F., Mccord, T. J., Shive, W.: Antitumor activity of some amino acid analogs. I. S-carbamylcysteine and Ó-carbazylserine. Texas Repts. Biol. Med. 16, 493–499 (1958).

    Google Scholar 

  • Skinner, C. G., Mckenna, G. F., Ross, D. L., Shive, W.: Antitumor activity of amino acid analogs. II. S - methyl carbamoyl -L - cysteine. Texas Rep. biol. Med. 19, 860–865 (1961).

    Google Scholar 

  • Skipper, H. E.: Effects of 6-mercaptopurine on experimental tumors. Ann. N.Y. Acad. Sci. 60, 267–272 (1954).

    Article  PubMed  CAS  Google Scholar 

  • Skipper, H. E., Bennett, L. L., Jr., Schabel, F. M., Jr.: Mechanism of action of azaserine. Fed. Proc. 13, 298–299 (1954).

    Google Scholar 

  • Skipper, H. E., Thomson, J. R.: A preliminary study of the influence of amino acid deficiencies on experimental cancer chemotherapy. In: Wolstenholme, G. E. W., O’connor, C. M. (Eds.): Ciba Foundation Symposium: Amino acids and peptides with antimetabolic activity, pp. 38–58. Boston: Little, Brown and Co. 1958.

    Google Scholar 

  • Slater, T. F., Sawyer, B. C.: Nicotinamide adenine dinucleotides in acute liver injury: effects of azaserine and puromycin in the rat. Biochem. Pharmacol. 15, 1267–1271 (1966).

    Article  CAS  Google Scholar 

  • Smtjlson, M. E., Neal, A. L.: Comparative effects of glutamine analogues on protein metabolism of 6C3H-ED and Ehrlich ascites carcinoma. Arch. Biochem. Biophys. 112, 25–31 (1965).

    Article  Google Scholar 

  • Speck, J. F.: The enzymatic synthesis of glutamine, a reaction utilizing adenosine triphosphate. J. biol. Chem. 179, 1405–1426 (1949).

    PubMed  CAS  Google Scholar 

  • Spencer, R. P., Bow, T. M., Markulis, M. A.: Intestinal transport of azaserine and NDO. Biochem. Pharmacol. 12, 599 (1963).

    Article  PubMed  CAS  Google Scholar 

  • Spencer, R. L., Preiss, J.: Biosynthesis of diphosphopyridine nucleotide. The purification and the properties of diphosphopyridine nucleotide synthetase from Escherichia coli B. J. biol. Chem. 242, 385–392 (1967).

    PubMed  CAS  Google Scholar 

  • Srinivasan, P. R., Rivera, A, Jr.: The enzymatic synthesis of anthranilate from shikimate 5-phosphate and L-glutamine. Biochemistry 2, 1059–1062 (1963).

    Article  PubMed  CAS  Google Scholar 

  • Srinivasan, P. R., Weiss, B.: The biosynthesis of p-aminobenzoic acid: studies on the origin of the amino group. Biochim. biophys. Acta (Amst.) 51, 597–599 (1961).

    Article  CAS  Google Scholar 

  • Steinman, I. D., Iyer, V. N., Szybalski, W.: The mechanism of chemical mutagenesis. II. Interactions of selected compounds with manganous chloride. Archives Biochem. Biophys. 76, 78–86 (1958).

    CAS  Google Scholar 

  • Sugiura, K.: Effect of L-asparaginase (NSC-109, 229) on transplantable and spontaneous tumors from mice and rats. Cancer Chemother. Rep. 53, 189–194 (1969).

    Google Scholar 

  • Szybalski, W.: Special microbiological systems. II. Observations on chemical mutagenesis in microorganisms. Ann. N.Y. Acad. Sci. 76, 475–489 (1958).

    PubMed  CAS  Google Scholar 

  • Tamir, H., Srinivasan, P. R.: Purification and properties of anthranilate synthetase from Salmonella typhimurium. J. biol. Chem. 244, 6507–6513 (1969).

    PubMed  CAS  Google Scholar 

  • Tanaka, N., Sashikata, K., Wada, T., Sugawara, S., Umezawa, H.: Mechanism of action of O-carbamyl-D-serine. J. Antibiot. (Tokyo) 16, 217–221 (1963).

    CAS  Google Scholar 

  • Tapia,R., Awapara, J.: Formation of y-aminobutyric acid (GABA) in brain of mice treated with L-glutamic acid-y-hydrazide and pyridoxal phosphate - y - glutamyl hydrazone. Proc. Soc. exp. Biol. (N.Y.) 126, 218–221 (1967).

    Google Scholar 

  • Tarnowski, G. S., Mountain, I. M., Stock, C. C.: Combination therapy of animal tumors with L-asparaginase and antagonists of glutamine or glutamic acid. Cancer Res. 30, 1118–1122 (1970).

    PubMed  CAS  Google Scholar 

  • Tarnowski, G. S., Stock, C. C.: Effects of combinations of azaserine and of 6-diazo-5-oxo-L- norleucine with purine analogs and other antimetabolites on the growth of two mouse mammary carcinomas. Cancer Res. 17, 1033–1039 (1957).

    PubMed  CAS  Google Scholar 

  • Terawaki, A., Greenberg, J.: Effect of some radiomimetic agents on deoxyribonucleic acid synthesis in Escherichia coli and transformation in Bacillus subtilis. Biochim. biophys. Acta (Amst.) 95, 170–173 (1965).

    CAS  Google Scholar 

  • Tews, J. K., Stone, W. E.: Effects of methionine sulfoximine on levels of free amino acids and related substances in brain. Biochem. Pharmacol. 13, 543–545 (1964).

    Article  PubMed  CAS  Google Scholar 

  • Thiersch, J. B.: Effect of 0-diazoaeetyl-L-serine on rat litter. Proc. Soc. exp. Biol. (N.Y.) 94, 27–32 (1957a).

    CAS  Google Scholar 

  • Thiersch, J. B.: Effect of 6-diazo-5-oxo-L-norleucine (DON) on the rat litter in utero. Proc. Soc. exp. Biol. (N.Y.) 94, 33–35 (1957b).

    CAS  Google Scholar 

  • Thiersch, J. B.: Effect of alazopeptin (A) on litter and fetus of the rat in utero. Proc. Soc. exp. Biol. (N.Y.) 97, 888–889 (1958).

    CAS  Google Scholar 

  • Tomisek, A. J., Kelly, H. J., Skipper, H. E.: Chromatographic studies of purine metabolism. I. The effect of azaserine on purine biosynthesis in E. coli using various C14-labeled precursors. Arch. Biochem. Biophys. 64, 437–455 (1956).

    Google Scholar 

  • Tomisek, A. J., Reid, M. R.: Chromatographic studies of purine metabolism. Y. Inhibition mechanism of diazo-oxo-norleueine in wild type and in diazo-oxonorleucine-resistant Escherichia coli. J. biol. Chem. 237, 807–811 (1962).

    PubMed  CAS  Google Scholar 

  • Tomisek, A. J., Reid, M. R., Skipper, H. E.: Chromatographic studies of purine metabolism. IV. Reversal of azaserine-induced inhibition by phenylalanine and tryptophan. Cancer Res. 19, 489–493 (1959).

    PubMed  CAS  Google Scholar 

  • Van Den Berg, C. J., Van Den Velden, J.: The effect of methionine sulphoximine on the incorporation of labelled glucose, acetate, phenylalanine and proline into glutamate and related amino acids in the brains of mice. J. Neurochem. 17, 985–991 (1970).

    Article  PubMed  Google Scholar 

  • Van Dermeulen, P. Y. F., Bassham, J. A.: Study of inhibition of azaserine and diazo-oxonorleueine (DON) on the algae Scenedesmus and Chlorella. J. Amer. chem. Soc. 81, 2233–2239 (1959).

    Article  Google Scholar 

  • Vandevoorde, J. P., Hansen, H. J., Nadler, S. B.: Metabolism of leukemic cells in culture; azaserine inhibition of J-128 (Osgood). Proc. Soc. exp. Biol. (N.Y.) 115, 55–57 (1964).

    CAS  Google Scholar 

  • Vogel, C. L., Calabresi, P.: Enhanced suppression of experimental allergic encephalomyelitis by combination chemotherapy with duazomycin-A and 6-mercaptopurine. Proc. Soc. exp. Biol. (N.Y.) 131, 251–256 (1969).

    CAS  Google Scholar 

  • Weiss, A. J., Ramirez, G., Grage, T., Strawitz, D., Goldman, L., Downing, V.: Phase II study of azotomycin (NSC 56654). Cancer Chemother. Repts. 52, 611–614 (1968).

    CAS  Google Scholar 

  • Westland, R. D., Fusari, S. A., Crooks, H. M., Jr.: 6-Diazo-5-oxo-L-norleucine, a new tumor- inhibitory substance. Synthetic studies. Amer. chem. Soc. 129th Meeting Abstr. 14 M (1956).

    Google Scholar 

  • Weygand, F., Bestmann, H. J., Klieger, E.: N-Trifluoracety 1 -aminosäuren. XI. Synthese des 6-diazo-5-oxo-L-norleucins und der 7-diazo-6-oxo-2-L-amino-önanthsäure. Chem. Ber. 91, 1037–1040 (1958).

    Article  CAS  Google Scholar 

  • Wilkoff, L. J., Wilcox, W. S., Burdeshaw, J. A., Dixon, G. J., Dulmadge, E. A.: Effect of antimetabolites on kinetic behavior of proliferating cultured L1210 leukemia cells. J. nat. Cancer Inst. 39, 965–975 (1967).

    PubMed  CAS  Google Scholar 

  • Woody, P. L., Mandell, J. D., Greenberg, J.: Resistance and cross-resistance of Escherichia coli mutants to anticancer agents. Radiat. Res. 15, 290–297 (1961).

    Article  PubMed  CAS  Google Scholar 

  • Woody-Karrer, P., Greenberg, J.: Resistance and cross resistance of Escherichia coli 8 mutants to the radiomimetic agent nitrofurazone. J. Bact. 85, 1208–1216 (1963).

    PubMed  CAS  Google Scholar 

  • Wtj, C., Ytjan, L. H.: Regulation of synthesis of glutamine synthetase in Escherichia coli. J. gen. Microbiol. 51, 57–65 (1968).

    Google Scholar 

  • Yarovaya, L. M., Mardashev, S. R., Debov, S. S.: Effect of some glutamine antimetabolites on the guanine monophosphate synthetase of Escherichia coli. Vop. med. Khim. 13, 176 to 180 (1967); Biol. Abstr. 49, 25139 (1969).

    Google Scholar 

  • Yip, M. C. M., Knox, W. E.: Glutamine-dependent carbamyl phosphate synthetase. J. biol. Chem. 245, 2199–2204 (1970).

    PubMed  CAS  Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1975 Springer-Verlag Berlin · Heidelberg

About this chapter

Cite this chapter

Bennett, L.L. (1975). Glutamine Antagonists. In: Sartorelli, A.C., Johns, D.G. (eds) Antineoplastic and Immunosuppressive Agents. Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology, vol 38 / 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-65806-8_24

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-65806-8_24

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-65808-2

  • Online ISBN: 978-3-642-65806-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics