Arginine Deiminase: Current Understanding and Applications

Page: [124 - 136] Pages: 13

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Abstract

Background: Arginine deiminase (ADI), an arginine catabolizing enzyme, is considered as an anti-tumor agent for the treatment of arginine auxotrophic cancers. However, some obstacles limit its clinical applications.

Objective: This review will summarize the clinical applications of ADI, from a brief history to its limitations, and will discuss the different ways to deal with the clinical limitations.

Method: The structure analysis, cloning, expression, protein engineering and applications of arginine deiminase enzyme have been explained in this review.

Conclusion: Recent patents on ADI are related to ADI engineering to increase its efficacy for clinical application. The intracellular delivery of ADI and combination therapy seem to be the future strategies in the treatment of arginine auxotrophic cancers. Applying ADIs with optimum features from different sources and or ADI engineering, are promising strategies to improve the clinical application of ADI.

Keywords: Arginine deiminase, anti-tumor, pegylation, targeted therapy, protein engineering, protein expression.

Graphical Abstract

[1]
Phillips MM, Sheaff MT, Szlosarek PW. Targeting arginine-dependent cancers with arginine-degrading enzymes: opportunities and challenges. Cancer Res Treat 2013; 45(4): 251-62.
[2]
Yoon JK, Frankel AE, Feun LG, Ekmekcioglu S, Kim KB. Arginine deprivation therapy for malignant melanoma. Clin Pharmacol 2013; 5: 11-9.
[3]
Synakiewicz A, Stachowicz-Stencel T, Adamkiewicz-Drozynska E. The role of arginine and the modified arginine deiminase enzyme ADI-PEG 20 in cancer therapy with special emphasis on Phase I/II clinical trials. Expert Opin Investig Drugs 2014; 23(11): 1517-29.
[4]
Zúñiga M, Pérez G, González-Candelas F. Evolution of arginine deiminase (ADI) pathway genes. Mol Phylogenet Evol 2002; 25(3): 429-44.
[5]
Novák L, Zubáčová Z, Karnkowska A, et al. Arginine deiminase pathway enzymes: evolutionary history in metamonads and other eukaryotes. BMC Evol Biol 2016; 16: 197.
[6]
Oginsky E, Gehrig R. The arginine dihydrolase system of Streptococcus faecalis. II. Properties of arginine desimidase. J Biol Chem 1952; 198(2): 799-805.
[7]
Zuniga M, Perez G, Gonzalez-Candelas F. Evolution of arginine deiminase (ADI) pathway genes. Mol Phylogenet Evol 2002; 25(3): 429-44.
[8]
Casiano-Colon A, Marquis RE. Role of the arginine deiminase system in protecting oral bacteria and an enzymatic basis for acid tolerance. Appl Environ Microbiol 1988; 54(6): 1318-24.
[9]
Marquis RE, Bender GR, Murray DR, Wong A. Arginine deiminase system and bacterial adaptation to acid environments. Appl Environ Microbiol 1987; 53(1): 198-200.
[10]
Vander Wauven C, Piérard A, Kley-Raymann M, Haas D. Pseudomonas aeruginosa mutants affected in anaerobic growth on arginine: evidence for a four-gene cluster encoding the arginine deiminase pathway. J Bacteriol 1984; 160(3): 928-34.
[11]
Hitzmann A, Bergmann S, Rohde M, Chhatwal GS, Fulde M. Identification and characterization of the arginine deiminase system of Streptococcus canis. Vet Microbiol 2013; 162(1): 270-7.
[12]
Cusumano ZT, Watson ME, Caparon MG. Streptococcus pyogenes Arginine and Citrulline Catabolism Promotes Infection and Modulates Innate Immunity. Infect Immun 2014; 82(1): 233-42.
[13]
Fulde M, Willenborg J, de Greeff A, et al. ArgR is an essential local transcriptional regulator of the arcABC operon in Streptococcus suis and is crucial for biological fitness in an acidic environment. Microbiology 2011; 157(Pt 2): 572-82.
[14]
Ryan S, Begley M, Gahan CG, Hill C. Molecular characterization of the arginine deiminase system in Listeria monocytogenes: regulation and role in acid tolerance. Environ Microbiol 2009; 11(2): 432-45.
[15]
Knodler LA, Schofield PJ, Gooley AA, Edwards MR. Giardia intestinalis: purification and Partial Amino Acid Sequence of Arginine Deiminase. Exp Parasitol 1997; 85(1): 77-80.
[16]
Knodler LA, Sekyere EO, Stewart TS, Schofield PJ, Edwards MR. Cloning and expression of a prokaryotic enzyme, arginine deiminase, from a primitive eukaryote Giardia intestinalis. J Biol Chem 1998; 273(8): 4470-7.
[17]
Bogdan C. Nitric oxide and the immune response. Nat Immunol 2001; 2(10): 907-16.
[18]
Mayer B, Hemmens B. Biosynthesis and action of nitric oxide in mammalian cells. Trends Biochem Sci 1997; 22(12): 477-81.
[19]
Horn F. The breakdown of arginine to citrulline by Bacillus pyocyaneus. Hoppe Seylers Z Physiol Chem 1933; 216: 244-7.
[20]
Galkin A, Kulakova L, Sarikaya E, Lim K, Howard A, Herzberg O. Structural insight into arginine degradation by arginine deiminase, an antibacterial and parasite drug target. J Biol Chem 2004; 279(14): 14001-8.
[21]
Lu X, Li L, Wu R, et al. Kinetic analysis of Pseudomonas aeruginosa arginine deiminase mutants and alternate substrates provides insight into structural determinants of function. Biochemistry 2006; 45(4): 1162-72.
[22]
Oudjama Y, Tricot C, Stalon V, Wouters J. Overexpression, purification, crystallization and preliminary X-ray crystallographic analysis of Pseudomonas aeruginosa L-arginine deiminase. Acta Crystallogr D Biol Crystallogr 2002; 58(Pt 12): 2150-2.
[23]
Galkin A, Lu X, Dunaway-Mariano D, Herzberg O. Crystal structures representing the Michaelis complex and the thiouronium reaction intermediate of Pseudomonas aeruginosa arginine deiminase. J Biol Chem 2005; 280(40): 34080-7.
[24]
Das K, Butler GH, Kwiatkowski V, Clark Jr A.D., Yadav P, Arnold E. Crystal structures of arginine deiminase with covalent reaction intermediates; implications for catalytic mechanism. Structure 2004; 12(4): 657-67.
[25]
Gallego P, Planell R, Benach J, Querol E, Perez-Pons JA, Reverter D. Structural characterization of the enzymes composing the arginine deiminase pathway in Mycoplasma penetrans. PLoS One 2012; 7(10): e47886.
[26]
Henningham A, Ericsson DJ, Langer K, et al. Structure-informed design of an enzymatically in-active vaccine component for group A Streptococcus. MBio 2013; 4(4): e00509-13.
[27]
Shirai H, Mokrab Y, Mizuguchi K. The guanidino‐group modifying enzymes: Structural basis for their diversity and commonality. Proteins 2006; 64(4): 1010-23.
[28]
Humm A, Fritsche E, Steinbacher S, Huber R. Crystal structure and mechanism of human L-arginine:glycine amidinotransferase: a mitochondrial enzyme involved in creatine biosynthesis. EMBO J 1997; 16(12): 3373-85.
[29]
Arita K, Hashimoto H, Shimizu T, Nakashima K, Yamada M, Sato M. Structural basis for Ca(2+)-induced activation of human PAD4. Nat Struct Mol Biol 2004; 11(8): 777-83.
[30]
Llacer JL, Polo LM, Tavarez S, Alarcon B, Hilario R, Rubio V. The gene cluster for agmatine catabolism of Enterococcus faecalis: study of recombinant putrescine transcarbamylase and agmatine deiminase and a snapshot of agmatine deiminase catalyzing its reaction. J Bacteriol 2007; 189(4): 1254-65.
[31]
Murray-Rust J, Leiper J, McAlister M, et al. Structural insights into the hydrolysis of cellular nitric oxide synthase inhibitors by dimethylarginine dimethylaminohydrolase. Nat Struct Biol 2001; 8(8): 679-83.
[32]
Kundu M, Thomas J, Fialho A, et al. The Anticancer Activity of the N-Terminal CARD-Like Domain of Arginine Deiminase (ADI) from Pseudomonas aeruginosa. Lett Drug Des Discov 2009; 6(6): 403-12.
[33]
Morris SM Jr. Arginine: beyond protein. Am J Clin Nutr 2006; 83(2): 508s-12s.
[34]
Dillon BJ, Prieto VG, Curley SA, et al. Incidence and distribution of argininosuccinate synthetase deficiency in human cancers: a method for identifying cancers sensitive to arginine deprivation. Cancer 2004; 100(4): 826-33.
[35]
Delage B, Fennell DA, Nicholson L, et al. Arginine deprivation and argininosuccinate synthetase expression in the treatment of cancer. Int J Cancer 2010; 126(12): 2762-72.
[36]
Muller HJ, Boos J. Use of L-asparaginase in childhood ALL. Crit Rev Oncol Hematol 1998; 28(2): 97-113.
[37]
Ghoshoon MB, Berenjian A, Hemmati S, et al. Extracellular production of recombinant L-Asparagi-nase II in Escherichia coli: Medium optimization using response surface methodology. Int J Pept Res Ther 2015; 21(4): 487-95.
[38]
Miyazaki K, Takaku H, Umeda M, et al. Potent growth inhibition of human tumor cells in culture by arginine deiminase purified from a culture medium of a Mycoplasma-infected cell line. Cancer Res 1990; 50(15): 4522-7.
[39]
Sugimura K, Fukuda S, Wada Y, et al. Identification and purification of arginine deiminase that originated from Mycoplasma arginini. Infect Immun 1990; 58(8): 2510-5.
[40]
Takaku H, Takase M, Abe S, Hayashi H, Miyazaki K. In vivo anti-tumor activity of arginine deiminase purified from Mycoplasma arginini. Int J Cancer 1992; 51(2): 244-9.
[41]
Takaku H, Matsumoto M, Misawa S, Miyazaki K. Anti-tumor activity of arginine deiminase from Mycoplasma argini and its growth-inhibitory mechanism. Jpn J Cancer Res 1995; 86(9): 840-6.
[42]
Wu B-W, Almassy R, He W, et al. Engineered chimeric pegylated adi and methods of use.US20170000862A1 2017.
[43]
Holtsberg FW, Ensor CM, Steiner MR, Bomalaski JS, Clark MA. Poly(ethylene glycol) (PEG) conjugated arginine deiminase: effects of PEG formulations on its pharmacological properties. J Control Release 2002; 80(1-3): 259-71.
[44]
Shen LJ, Shen WC. Drug evaluation: ADI-PEG-20--a PEGylated arginine deiminase for arginine-auxotrophic cancers. Curr Opin Mol Ther 2006; 8(3): 240-8.
[45]
Ascierto PA, Scala S, Castello G, et al. Pegylated arginine deiminase treatment of patients with metastatic melanoma: results from phase I and II studies. J Clin Oncol 2005; 23(30): 7660-8.
[46]
Feun LG, Marini A, Walker G, et al. Negative argininosuccinate synthetase expression in melanoma tumours may predict clinical benefit from arginine-depleting therapy with pegylated arginine deiminase. Br J Cancer 2012; 106(9): 1481-5.
[47]
Ott PA, Carvajal RD, Pandit-Taskar N, et al. Phase I/II study of pegylated arginine deiminase (ADI-PEG 20) in patients with advanced melanoma. Invest New Drugs 2013; 31(2): 425-34.
[48]
Izzo F, Marra P, Beneduce G, et al. Pegylated arginine deiminase treatment of patients with unresectable hepatocellular carcinoma: results from phase I/II studies. J Clin Oncol 2004; 22(10): 1815-22.
[49]
Glazer ES, Piccirillo M, Albino V, et al. Phase II study of pegylated arginine deiminase for nonresectable and metastatic hepatocellular carcinoma. J Clin Oncol 2010; 28(13): 2220-6.
[50]
Yang TS, Lu SN, Chao Y, et al. A randomised phase II study of pegylated arginine deiminase (ADI-PEG 20) in Asian advanced hepatocellular carcinoma patients. Br J Cancer 2010; 103(7): 954-60.
[51]
Kim RH, Coates JM, Bowles TL, et al. Arginine deiminase as a novel therapy for prostate cancer induces autophagy and caspase-independent apoptosis. Cancer Res 2009; 69(2): 700-8.
[52]
Tsai WB, Aiba I, Lee SY, Feun L, Savaraj N, Kuo MT. Resistance to arginine deiminase treatment in melanoma cells is associated with induced argininosuccinate synthetase expression involving c-Myc/HIF-1alpha/Sp4. Mol Cancer Ther 2009; 8(12): 3223-33.
[53]
Synakiewicz A, Stachowicz-Stencel T, Adamkiewicz-Drozynska E. The role of arginine and the modified arginine deiminase enzyme ADI-PEG 20 in cancer therapy with special emphasis on Phase I/II clinical trials. Expert Opin Investig Drugs 2014; 23(11): 1517-29.
[54]
Lowery MA, Yu KH, Kelsen DP, et al. A phase 1/1B trial of ADI-PEG 20 plus nab-paclitaxel and gemcitabine in patients with advanced pancreatic adenocarcinoma. Cancer 2017; 123(23): 4556-65.
[55]
Beddowes E, Spicer J, Chan PY, et al. Phase 1 Dose-Escalation Study of Pegylated Arginine Deiminase, Cisplatin, and Pemetrexed in Patients With Argininosuccinate Synthetase 1-Deficient Thoracic Cancers. J Clin Oncol 2017; 35(16): 1778-85.
[56]
Long Y, Tsai WB, Chang JT, et al. Cisplatin-induced synthetic lethality to arginine-starvation therapy by transcriptional suppression of ASS1 is regulated by DEC1, HIF-1alpha, and c-Myc transcription network and is independent of ASS1 promoter DNA methylation. Oncotarget 2016; 7(50): 82658-70.
[57]
Savaraj N, Wu C, Li YY, et al. Targeting argininosuccinate synthetase negative melanomas using combination of arginine degrading enzyme and cisplatin. Oncotarget 2015; 6(8): 6295-309.
[58]
Daylami R, Muilenburg DJ, Virudachalam S, Bold RJ. Pegylated arginine deiminase synergistically increases the cytotoxicity of gemcitabine in human pancreatic cancer. J Exp Clin Cancer Res 2014; 33: 102.
[59]
Tomlinson BK, Thomson JA, Bomalaski JS, et al. Phase I trial of arginine deprivation therapy with ADI-PEG 20 plus docetaxel in patients with advanced malignant solid tumors. Clin Cancer Res 2015; 21(11): 2480-6.
[60]
Wu FL, Yeh TH, Chen YL, et al. Intracellular delivery of recombinant arginine deiminase (rADI) by heparin-binding hemagglutinin adhesion peptide restores sensitivity in rADI-resistant cancer cells. Mol Pharm 2014; 11(8): 2777-86.
[61]
Yeh TH, Chen YR, Chen SY, et al. Selective intracellular delivery of recombinant arginine deiminase (ADI) using pH-sensitive cell penetrating peptides to overcome ADI resistance in hypoxic breast cancer cells. Mol Pharm 2016; 13(1): 262-71.
[62]
Kubo M, Nishitsuji H, Kurihara K, Hayashi T, Masuda T, Kannagi M. Suppression of human immunodeficiency virus type 1 replication by arginine deiminase of Mycoplasma arginini. J Gen Virol 2006; 87(Pt 6): 1589-93.
[63]
Izzo F, Montella M, Orlando AP, et al. Pegylated arginine deiminase lowers hepatitis C viral titers and inhibits nitric oxide synthesis. J Gastroenterol Hepatol 2007; 22(1): 86-91.
[64]
Trejo-Soto PJ, Aguayo-Ortiz R, Yepez-Mulia L, Hernandez-Campos A, Medina-Franco JL, Castillo R. Insights into the structure and inhibition of Giardia intestinalis arginine deiminase: homology modeling, docking, and molecular dynamics studies. J Biomol Struct Dyn 2016; 34(4): 732-48.
[65]
Stasyuk NY, Gayda GZ, Fayura LR, Boretskyy YR, Gonchar MV, Sibirny AA. Novel arginine deiminase-based method to assay L-arginine in beverages. Food Chem 2016; 201: 320-6.
[66]
Song W, Sun X, Chen X, Liu D, Liu L. Enzymatic production of l-citrulline by hydrolysis of the guanidinium group of l-arginine with recombinant arginine deiminase. J Biotechnol 2015; 208: 37-43.
[67]
Akashi K, Miyake C, Yokota A. Citrulline, a novel compatible solute in drought‐tolerant wild watermelon leaves, is an efficient hydroxyl radical scavenger. FEBS Lett 2001; 508(3): 438-42.
[68]
Wiesinger H. Arginine metabolism and the synthesis of nitric oxide in the nervous system. Prog Neurobiol 2001; 64(4): 365-91.
[69]
David A, Gaynor J, Zis P, et al. An association of lower serum citrulline levels within 30 days of acute rejection in patients following small intestine transplantation. Transplant Proc 2006; 38(6): 1731-2.
[70]
Gondolesi G, Fishbein T, Chehade M, et al. Serum citrulline is a potential marker for rejection of intestinal allografts. Transplant Proc 2002; 34(3): 918-20.
[71]
Amer MN, Mansour NM, El-Diwany AI, Dawoud IE, Rasha FM. Isolation of probiotic lactobacilli strains harboring L-asparaginase and arginine deiminase genes from human infant feces for their potential application in cancer prevention. Ann Microbiol 2013; 63: 1121-9.
[72]
Sharma A, Bala K, Husain I. Preliminary evaluation of arginine deiminase activity of indigenous bacterial strains for suitable chemotherapeutic applications. Biocatal Agric Biotechnol 2017; 12: 66-77.
[73]
El-Sayed AS, Hassan MN, Nada HM. Purification, immobilization, and biochemical characterization of l-arginine deiminase from thermophilic Aspergillus fumigatus KJ434941: anticancer activity in vitro. Biotechnol Prog 2015; 31(2): 396-405.
[74]
Misawa S, Aoshima M, Takaku H, Matsumoto M, Hayashi H. High-level expression of Mycoplasma arginine deiminase in Escherichia coli and its efficient renaturation as an anti-tumor enzyme. J Biotechnol 1994; 36(2): 145-55.
[75]
Song JA, Lee DS, Park JS, Han KY, Lee J. A novel Escherichia coli solubility enhancer protein for fusion expression of aggregation-prone heterologous proteins. Enzyme Microb Technol 2011; 49(2): 124-30.
[76]
Kang YS, Song JA, Han KY, Lee J. Escherichia coli EDA is a novel fusion expression partner to improve solubility of aggregation-prone heterologous proteins. J Biotechnol 2015; 194: 39-47.
[77]
Ahn KY, Lee B, Han KY, Song JA, Lee DS, Lee J. Synthesis of Mycoplasma arginine deiminase in E. coli using stress-responsive proteins. Enzyme Microb Technol 2014; 63: 46-9.
[78]
Su L, Woodard RW, Chen J, Wu J. Extracellular location of Thermobifida fusca cutinase expressed in Escherichia coli BL21 (DE3) without mediation of a signal peptide. Appl Environ Microbiol 2013; 79(14): 4192-8.
[79]
Su L, Ma Y, Wu J. Extracellular expression of natural cytosolic arginine deiminase from Pseudomonas putida and its application in the production of l-citrulline. Bioresour Technol 2015; 196: 176-83.
[80]
Wang Y, Li YZ. Cultivation to improve in vivo solubility of overexpressed arginine deiminases in Escherichia coli and the enzyme characteristics. BMC Biotechnol 2014; 14: 53.
[81]
Zarei M, Nezafat N, Morowvat MH, et al. Medium optimization for recombinant soluble arginine deiminase expression in Escherichia coli using response surface methodology. Curr Pharm Biotechnol 2017; 18(11): 935-41.
[82]
Zarei M, Nezafat N, Rahbar MR, et al. Decreasing the immunogenicity of arginine deiminase enzyme via structure‐based computational analysis. J Biomol Struct Dyn 2019; 37(2): 523-36.
[83]
Zhu L, Tee KL, Roccatano D, et al. Directed evolution of an antitumor drug (arginine deiminase PpADI) for increased activity at physiological pH. ChemBioChem 2010; 11(5): 691-7.
[84]
Zhu L, Verma R, Roccatano D, Ni Y, Sun ZH, Schwaneberg U. A potential antitumor drug (arginine deiminase) reengineered for efficient operation under physiological conditions. ChemBioChem 2010; 11(16): 2294-301.
[85]
Cheng F, Zhu L, Lue H, Bernhagen J, Schwaneberg U. Directed arginine deiminase evolution for efficient inhibition of arginine-auxotrophic melanomas. Appl Microbiol Biotechnol 2015; 99(3): 1237-47.
[86]
Cheng F, Yang J, Bocola M, Schwaneberg U, Zhu L. Loop engineering reveals the importance of active-site-decorating loops and gating residue in substrate affinity modulation of arginine deiminase (an anti-tumor enzyme). Biochem Biophys Res Commun 2018; 499(2): 233-8.
[87]
Jamil S, Liu MH, Liu YM, Han RZ, Xu GC, Ni Y. Hydrophobic mutagenesis and semi-rational engineering of arginine deiminase for markedly enhanced stability and catalytic efficiency. Appl Biochem Biotechnol 2015; 176(5): 1335-50.
[88]
Huang Y, Qiu J, Fu X, Fan M, Wang Y, Wang Y. Arginine deiminase mutant and preparation and application thereof. US8663967B2, 2014.
[89]
Godfrin Y, Goineau P-O. Erythrocytes containing arginine deiminase. US9968663B2, 2015.
[90]
Liu Y-M, Sun Z-H, Ni Y, Zheng P, Liu Y-P, Meng F-J. Isolation and identification of an arginine deiminase producing strain Pseudomonas plecoglossicida CGMCC2039. World J Microbiol Biotechnol 2008; 24(10): 2213-9.
[91]
Ni Y, Li Z, Sun Z, et al. Expression of arginine deiminase from Pseudomonas plecoglossicida CGMCC2039 in Escherichia coli and its anti-tumor activity. Curr Microbiol 2009; 58(6): 593-8.
[92]
Ding H, Liu H, Yin Y, et al. Insights into the modulation of optimum pH by a single histidine residue in arginine deiminase from Pseudomonas aeruginosa. Biol Chem 2012; 393(9): 1013-24.
[93]
Shibatani T, Kakimoto T, Chibata I. Crystallization and properties of L-arginine deiminase of Pseudomonas putida. J Biol Chem 1975; 250(12): 4580-3.
[94]
Manca de Nadra M, Pesce de Ruiz Holgado A, Oliver G. Isolation and properties of arginine deiminase in Lactobacillus buchneri NCDO110. J Appl Biochem 1984; 6(3): 184-7.
[95]
Park B-S, Hirotani A, Nakano Y, Kitaoka S. Purification and Some Properties of Arginine Deiminase in Euglena gracilis Z. Agric Biol Chem 1984; 48(2): 483-9.
[96]
Baur H, Luethi E, Stalon V, Mercenier A, Haas D. Sequence analysis and expression of the arginine-deiminase and carbamate-kinase genes of Pseudomonas aeruginosa. Eur J Biochem 1989; 179(1): 53-60.
[97]
Monstadt GM, Holldorf AW. Arginine deiminase from Halobacterium salinarium. Purification and properties. Biochem J 1991; 273: 739-45.
[98]
Knodler LA, Schofield PJ, Gooley AA, Edwards MR. Giardia intestinalis: purification and partial amino acid sequence of arginine deiminase. Exp Parasitol 1997; 85(1): 77-80.
[99]
Kim JE, Jeong DW, Lee HJ. Expression, purification, and characterization of arginine deiminase from Lactococcus lactis ssp. lactis ATCC 7962 in Escherichia coli BL21. Protein Expr Purif 2007; 53(1): 9-15.
[100]
Li L, Li Z, Chen D, et al. Inactivation of microbial arginine deiminases by L-canavanine. J Am Chem Soc 2008; 130(6): 1918-31.
[101]
Jiang H, Huang K, Mu W, Jiang B, Zhang T. Characterization of a recombinant arginine deiminase from Enterococcus faecalis SK32. 001 for L-citrulline production. Process Biochem 2018; 64: 136-42.
[102]
Burne RA, Parsons DT, Marquis RE. Cloning and expression in Escherichia coli of the genes of the arginine deiminase system of Streptococcus sanguis NCTC 10904. Infect Immun 1989; 57(11): 3540-8.
[103]
Beloussow K, Wang L, Wu J, Ann D, Shen WC. Recombinant arginine deiminase as a potential anti-angiogenic agent. Cancer Lett 2002; 183(2): 155-62.
[104]
Ensor CM, Holtsberg FW, Bomalaski JS, Clark MA. Pegylated arginine deiminase (ADI-SS PEG20,000 mw) inhibits human melanomas and hepatocellular carcinomas in vitro and in vivo. Cancer Res 2002; 62(19): 5443-50.
[105]
Wei Y, Zhou H, Sun Y, He Y, Luo Y. Insight into the catalytic mechanism of arginine deiminase: functional studies on the crucial sites. Proteins 2007; 66(3): 740-50.
[106]
Kozai M, Sasamori E, Fujihara M, Yamashita T, Taira H, Harasawa R. Growth inhibition of human melanoma cells by a recombinant arginine deiminase expressed in Escherichia coli. J Vet Med Sci 2009; 71(10): 1343-7.