Enzyme which catalyzes the hydrolysis of l-asparagine to l-aspartic acid and ammonia. Inhibits the growth of tumor cells requiring exogenous asparagine. Widely distributed; occurs in bacteria, fungi, yeasts, plants, animal tissues and guinea pig serum. Commonly obtained from E. coli and Erwinia sp. l-Asparaginase from E. coli has a mol wt of ≈136,000 and is composed of four identical subunits. Identification of antitumor activity: J. D. Broome, Nature 191, 1114 (1961); idem, J. Exp. Med. 118, 99 (1963). Purif, chemical properties of asparaginase from E. coli: D. H. Ho et al., J. Biol. Chem. 245, 3708 (1970). Structural studies: A. C. Greenquist, J. C. Wriston, Arch. Biochem. Biophys. 152, 280 (1972). Amino acid sequence: T. Maita et al., J. Biochem. 76, 1351 (1974). Pharmacology and clinical effects: R. H. Adamson, S. Fabro, Cancer Chemother. Rep. Part 1 52, 617 (1968); R. L. Capizzi et al., Annu. Rev. Med. 21, 433 (1970). Reviews: R. L. Capizzi, Leuk. Lymphoma 10, Suppl., 147-150 (1993); M. J. Keating et al., ibid. 153-157. Review of development, pharmacology, and clinical experience in leukemia: U. K. Narta et al., Crit. Rev. Oncol. Hematol. 61, 208-221 (2007); of sources, structural modification, and chemotherapeutic potential: N. Verma et al., Crit. Rev. Biotechnol. 27, 45-62 (2007).
l-Asparaginase from E. coli covalently coupled to polyethylene glycol moieties of mol wt ≈5000 Da. Prepn: F. F. Davis et al., DE 2433883 (1976 to Research Corp.); eidem, US 4179337 (1979). Prepn, pharmacology and antitumor efficacy: A. Abuchowski et al., Cancer Biochem. Biophys. 7, 175 (1984). Toxicology: A. T. Viau et al., Am. J. Vet. Res. 47, 1398 (1986). Review of clinical experience: F. Fuertges, A. Abuchowski, J. Controlled Release 11, 139 (1990). Review of clinical experience and therapeutic potential of intravenous administration: C. H. Fu, K. M. Sakamoto, Expert Opin. Pharmacother. 8, 1977-1984 (2007).
Antineoplastic (acute leukemia).
Antineoplastic; Enzymes