[en] Arginase-1 (ARG-1) is a promising target for cancer immunotherapy, but the small size and the highly polar nature of its catalytic site present significant challenges for inhibitor development. An alternative strategy to induce enzyme inhibition by targeting protein oligomerization has been developed recently, offering several advantages such as increased selectivity, promotion of protein degradation, and potential substoichiometric inhibition. In this study, we demonstrated that only trimeric ARG-1 is active, which was confirmed by producing monomeric arginase-1. Through in silico-driven site-directed mutagenesis, we identified an allosteric site involving five key amino acids responsible for ARG-1 trimerization. We further demonstrated the covalent modification of a key arginine residue within this pocket using phenylglyoxal disrupted ARG-1 oligomerization. Although phenylglyoxal has limited potency, it effectively supports the concept of ARG-1 inhibition via homomeric disruption, validating this allosteric targeting approach.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Dechenne, Juhans ; Louvain Drug Research Institute (LDRI), Medicinal Chemistry Research Group (CMFA), Université Catholique de Louvain (UCLouvain), Brussels B-1200, Belgium
Wierzbicka, Magdalena ; Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments
Krimou, Reda; Louvain Drug Research Institute (LDRI), Medicinal Chemistry Research Group (CMFA), Université Catholique de Louvain (UCLouvain), Brussels B-1200, Belgium
El Aakchioui, Asia; Louvain Drug Research Institute (LDRI), Medicinal Chemistry Research Group (CMFA), Université Catholique de Louvain (UCLouvain), Brussels B-1200, Belgium
Malo Pueyo, Julia; VIB-VUB Center for Structural Biology, Vlaams Instituut Voor Biotechnologie, Brussels B-1050, Belgium ; Brussels Center for Redox Biology, Vrije Universiteit Brussel, Brussels B-1050, Belgium ; Structural Biology Brussels, Vrije Universiteit Brussel, Brussels B-1050, Belgium
Messens, Joris; VIB-VUB Center for Structural Biology, Vlaams Instituut Voor Biotechnologie, Brussels B-1050, Belgium ; Brussels Center for Redox Biology, Vrije Universiteit Brussel, Brussels B-1050, Belgium ; Structural Biology Brussels, Vrije Universiteit Brussel, Brussels B-1050, Belgium
Fillet, Marianne ; Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments
Spillier, Quentin; Louvain Drug Research Institute (LDRI), Medicinal Chemistry Research Group (CMFA), Université Catholique de Louvain (UCLouvain), Brussels B-1200, Belgium
Frédérick, Raphaël ; Louvain Drug Research Institute (LDRI), Medicinal Chemistry Research Group (CMFA), Université Catholique de Louvain (UCLouvain), Brussels B-1200, Belgium
Language :
English
Title :
Examining Arginase-1 Trimerization Uncovers a Promising Allosteric Site for Inhibition.
FWB - Fédération Wallonie-Bruxelles F.R.S.-FNRS - Fonds de la Recherche Scientifique
Funding text :
This work was supported by the Belgian Fonds National de la Recherche Scientifique (F.R.S.- FNRS Grant T008223F and the French Community of Belgium (ARC 21/26-115). The authors thank Gael Cobraiville for his contribution to the LC-MS experiments.
Grzywa, T. M.; Sosnowska, A.; Matryba, P.; Rydzynska, Z.; Jasinski, M.; Nowis, D.; Golab, J. Myeloid Cell-Derived Arginase in Cancer Immune Response. Front Immunol 2020, 11 ( May), 938, 10.3389/fimmu.2020.00938
Christianson, D. W. Arginase: structure, mechanism, and physiological role in male and female sexual arousal. Acc. Chem. Res. 2005, 38 ( 3), 191- 201, 10.1021/ar040183k
Caldwell, R. W.; Rodriguez, P. C.; Toque, H. A.; Narayanan, S. P.; Caldwell, R. B. Arginase: A Multifaceted Enzyme Important in Health and Disease. Physiol Rev. 2018, 98 ( 2), 641- 665, 10.1152/physrev.00037.2016
Bagnost, T.; Ma, L.; da Silva, R. F.; Rezakhaniha, R.; Houdayer, C.; Stergiopulos, N.; Andre, C.; Guillaume, Y.; Berthelot, A.; Demougeot, C. Cardiovascular effects of arginase inhibition in spontaneously hypertensive rats with fully developed hypertension. Cardiovasc. Res. 2010, 87 ( 3), 569- 577, 10.1093/cvr/cvq081
Chen, B.; Calvert, A. E.; Cui, H.; Nelin, L. D. Hypoxia promotes human pulmonary artery smooth muscle cell proliferation through induction of arginase. Am. J. Physiol Lung Cell Mol. Physiol 2009, 297 ( 6), L1151- 1159, 10.1152/ajplung.00183.2009
Bakshi, N.; Morris, C. R. The role of the arginine metabolome in pain: implications for sickle cell disease. J. Pain Res. 2016, 9, 167- 175, 10.2147/JPR.S55571
Bagi, Z.; Feher, A.; Dou, H.; Broskova, Z. Selective up-regulation of arginase-1 in coronary arteries of diabetic patients. Front Immunol 2013, 4, 293, 10.3389/fimmu.2013.00293
Gonon, A. T.; Jung, C.; Katz, A.; Westerblad, H.; Shemyakin, A.; Sjoquist, P. O.; Lundberg, J. O.; Pernow, J. Local arginase inhibition during early reperfusion mediates cardioprotection via increased nitric oxide production. PLoS One 2012, 7 ( 7), e42038 10.1371/journal.pone.0042038
Berkowitz, D. E.; White, R.; Li, D.; Minhas, K. M.; Cernetich, A.; Kim, S.; Burke, S.; Shoukas, A. A.; Nyhan, D.; Champion, H. C.; Hare, J. M. Arginase reciprocally regulates nitric oxide synthase activity and contributes to endothelial dysfunction in aging blood vessels. Circulation 2003, 108 ( 16), 2000- 2006, 10.1161/01.CIR.0000092948.04444.C7
Cox, J. D.; Kim, N. N.; Traish, A. M.; Christianson, D. W. Arginase-boronic acid complex highlights a physiological role in erectile function. Nat. Struct. Biol. 1999, 6 ( 11), 1043- 1047, 10.1038/14929
Petrone, A. B.; O’Connell, G. C.; Regier, M. D.; Chantler, P. D.; Simpkins, J. W.; Barr, T. L. The Role of Arginase 1 in Post-Stroke Immunosuppression and Ischemic Stroke Severity. Transl Stroke Res. 2016, 7 ( 2), 103- 110, 10.1007/s12975-015-0431-9
Hansmannel, F.; Sillaire, A.; Kamboh, M. I.; Lendon, C.; Pasquier, F.; Hannequin, D.; Laumet, G.; Mounier, A.; Ayral, A. M.; DeKosky, S. T. Is the urea cycle involved in Alzheimer’s disease?. J. Alzheimers Dis 2010, 21 ( 3), 1013- 1021, 10.3233/JAD-2010-100630
Cantoni, C.; Cignarella, F.; Ghezzi, L.; Mikesell, B.; Bollman, B.; Berrien-Elliott, M. M.; Ireland, A. R.; Fehniger, T. A.; Wu, G. F.; Piccio, L. Mir-223 regulates the number and function of myeloid-derived suppressor cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Acta Neuropathol 2017, 133 ( 1), 61- 77, 10.1007/s00401-016-1621-6
Elms, S. C.; Toque, H. A.; Rojas, M.; Xu, Z.; Caldwell, R. W.; Caldwell, R. B. The role of arginase I in diabetes-induced retinal vascular dysfunction in mouse and rat models of diabetes. Diabetologia 2013, 56 ( 3), 654- 662, 10.1007/s00125-012-2789-5
Bron, L.; Jandus, C.; Andrejevic-Blant, S.; Speiser, D. E.; Monnier, P.; Romero, P.; Rivals, J. P. Prognostic value of arginase-II expression and regulatory T-cell infiltration in head and neck squamous cell carcinoma. Int. J. Cancer 2013, 132 ( 3), E85- 93, 10.1002/ijc.27728
Ma, Z.; Lian, J.; Yang, M.; Wuyang, J.; Zhao, C.; Chen, W.; Liu, C.; Zhao, Q.; Lou, C.; Han, J.; Zhang, Y. Overexpression of Arginase-1 is an indicator of poor prognosis in patients with colorectal cancer. Pathol Res. Pract 2019, 215 ( 6), 152383 10.1016/j.prp.2019.03.012
Czystowska-Kuzmicz, M.; Sosnowska, A.; Nowis, D.; Ramji, K.; Szajnik, M.; Chlebowska-Tuz, J.; Wolinska, E.; Gaj, P.; Grazul, M.; Pilch, Z. Small extracellular vesicles containing arginase-1 suppress T-cell responses and promote tumor growth in ovarian carcinoma. Nat. Commun. 2019, 10 ( 1), 3000, 10.1038/s41467-019-10979-3
Ren, W.; Zhang, X.; Li, W.; Feng, Q.; Feng, H.; Tong, Y.; Rong, H.; Wang, W.; Zhang, D.; Zhang, Z.; Tu, S. Circulating and tumor-infiltrating arginase 1-expressing cells in gastric adenocarcinoma patients were mainly immature and monocytic Myeloid-derived suppressor cells. Sci. Rep 2020, 10 ( 1), 8056, 10.1038/s41598-020-64841-4
Mussai, F.; Egan, S.; Hunter, S.; Webber, H.; Fisher, J.; Wheat, R.; McConville, C.; Sbirkov, Y.; Wheeler, K.; Bendle, G. Neuroblastoma Arginase Activity Creates an Immunosuppressive Microenvironment That Impairs Autologous and Engineered Immunity. Cancer Res. 2015, 75 ( 15), 3043- 3053, 10.1158/0008-5472.CAN-14-3443
Mussai, F.; De Santo, C.; Abu-Dayyeh, I.; Booth, S.; Quek, L.; McEwen-Smith, R. M.; Qureshi, A.; Dazzi, F.; Vyas, P.; Cerundolo, V. Acute myeloid leukemia creates an arginase-dependent immunosuppressive microenvironment. Blood 2013, 122 ( 5), 749- 758, 10.1182/blood-2013-01-480129
de Boniface, J.; Mao, Y.; Schmidt-Mende, J.; Kiessling, R.; Poschke, I. Expression patterns of the immunomodulatory enzyme arginase 1 in blood, lymph nodes and tumor tissue of early-stage breast cancer patients. Oncoimmunology 2012, 1 ( 8), 1305- 1312, 10.4161/onci.21678
Rotondo, R.; Barisione, G.; Mastracci, L.; Grossi, F.; Orengo, A. M.; Costa, R.; Truini, M.; Fabbi, M.; Ferrini, S.; Barbieri, O. IL-8 induces exocytosis of arginase 1 by neutrophil polymorphonuclears in nonsmall cell lung cancer. Int. J. Cancer 2009, 125 ( 4), 887- 893, 10.1002/ijc.24448
Li, J. H.; Zhang, S. Q.; Qiu, X. G.; Zhang, S. J.; Zheng, S. H.; Zhang, D. H. Long non-coding RNA NEAT1 promotes malignant progression of thyroid carcinoma by regulating miRNA-214. Int. J. Oncol. 2017, 50 ( 2), 708- 716, 10.3892/ijo.2016.3803
Andrade, L. N. S.; Otake, A. H.; Cardim, S. G. B.; da Silva, F. I.; Ikoma Sakamoto, M. M.; Furuya, T. K.; Uno, M.; Pasini, F. S.; Chammas, R. Extracellular Vesicles Shedding Promotes Melanoma Growth in Response to Chemotherapy. Sci. Rep 2019, 9 ( 1), 14482, 10.1038/s41598-019-50848-z
You, J.; Chen, W.; Chen, J.; Zheng, Q.; Dong, J.; Zhu, Y. The Oncogenic Role of ARG1 in Progression and Metastasis of Hepatocellular Carcinoma. BioMed Res. Int. 2018, 2018, 2109865 10.1155/2018/2109865
Rodriguez, P. C.; Ernstoff, M. S.; Hernandez, C.; Atkins, M.; Zabaleta, J.; Sierra, R.; Ochoa, A. C. Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res. 2009, 69 ( 4), 1553- 1560, 10.1158/0008-5472.CAN-08-1921
Sippel, T. R.; White, J.; Nag, K.; Tsvankin, V.; Klaassen, M.; Kleinschmidt-DeMasters, B. K.; Waziri, A. Neutrophil degranulation and immunosuppression in patients with GBM: restoration of cellular immune function by targeting arginase I. Clin. Cancer Res. 2011, 17 ( 22), 6992- 7002, 10.1158/1078-0432.CCR-11-1107
Bronte, V.; Serafini, P.; Mazzoni, A.; Segal, D. M.; Zanovello, P. L-arginine metabolism in myeloid cells controls T-lymphocyte functions. Trends Immunol. 2003, 24 ( 6), 301- 305, 10.1016/S1471-4906(03)00132-7
Borek, B.; Gajda, T.; Golebiowski, A.; Blaszczyk, R. Boronic acid-based arginase inhibitors in cancer immunotherapy. Bioorg. Med. Chem. 2020, 28 ( 18), 115658 10.1016/j.bmc.2020.115658
Failla, M.; Molaro, M. C.; Schiano, M. E.; Serafini, M.; Tiburtini, G. A.; Gianquinto, E.; Scoccia, R.; Battisegola, C.; Rimoli, M. G.; Chegaev, K. Opportunities and Challenges of Arginase Inhibitors in Cancer: A Medicinal Chemistry Perspective. J. Med. Chem. 2024, 67 ( 22), 19988- 20021, 10.1021/acs.jmedchem.4c01429
Steggerda, S. M.; Bennett, M. K.; Chen, J.; Emberley, E.; Huang, T.; Janes, J. R.; Li, W.; MacKinnon, A. L.; Makkouk, A.; Marguier, G. Inhibition of arginase by CB-1158 blocks myeloid cell-mediated immune suppression in the tumor microenvironment. J. Immunother Cancer 2017, 5 ( 1), 101, 10.1186/s40425-017-0308-4
Nishi, H.; Hashimoto, K.; Madej, T.; Panchenko, A. R. Evolutionary, physicochemical, and functional mechanisms of protein homooligomerization. Prog. Mol. Biol. Transl Sci. 2013, 117, 3- 24, 10.1016/B978-0-12-386931-9.00001-5
Thabault, L.; Liberelle, M.; Frederick, R. Targeting protein self-association in drug design. Drug Discov Today 2021, 26 ( 5), 1148- 1163, 10.1016/j.drudis.2021.01.028
Wells, S. A.; van der Kamp, M. W.; McGeagh, J. D.; Mulholland, A. J. Structure and Function in Homodimeric Enzymes: Simulations of Cooperative and Independent Functional Motions. PLoS One 2015, 10 ( 8), e0133372 10.1371/journal.pone.0133372
Levy, E. D.; Pereira-Leal, J. B.; Chothia, C.; Teichmann, S. A. 3D complex: a structural classification of protein complexes. PLoS Comput. Biol. 2006, 2 ( 11), e155 10.1371/journal.pcbi.0020155
Jubb, H. C.; Pandurangan, A. P.; Turner, M. A.; Ochoa-Montano, B.; Blundell, T. L.; Ascher, D. B. Mutations at protein-protein interfaces: Small changes over big surfaces have large impacts on human health. Prog. Biophys. Mol. Biol. 2017, 128, 3- 13, 10.1016/j.pbiomolbio.2016.10.002
Anastassiadis, T.; Deacon, S. W.; Devarajan, K.; Ma, H.; Peterson, J. R. Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat. Biotechnol. 2011, 29 ( 11), 1039- 1045, 10.1038/nbt.2017
Gunderwala, A. Y.; Nimbvikar, A. A.; Cope, N. J.; Li, Z.; Wang, Z. Development of Allosteric BRAF Peptide Inhibitors Targeting the Dimer Interface of BRAF. ACS Chem. Biol. 2019, 14 ( 7), 1471- 1480, 10.1021/acschembio.9b00191
Kubota, H. Quality control against misfolded proteins in the cytosol: a network for cell survival. J. Biochem 2009, 146 ( 5), 609- 616, 10.1093/jb/mvp139
Joshi, R. G.; Kulkarni, S.; Ratna Prabha, C. Engineering degrons of yeast ornithine decarboxylase as vehicles for efficient targeted protein degradation. Biochim. Biophys. Acta 2015, 1850 ( 12), 2452- 2463, 10.1016/j.bbagen.2015.09.003
Pi, F.; Vieweger, M.; Zhao, Z.; Wang, S.; Guo, P. Discovery of a new method for potent drug development using power function of stoichiometry of homomeric biocomplexes or biological nanomotors. Expert Opin Drug Deliv 2016, 13 ( 1), 23- 36, 10.1517/17425247.2015.1082544
Kanyo, Z. F.; Scolnick, L. R.; Ash, D. E.; Christianson, D. W. Structure of a unique binuclear manganese cluster in arginase. Nature 1996, 383 ( 6600), 554- 557, 10.1038/383554a0
Sabio, G.; Mora, A.; Rangel, M. A.; Quesada, A.; Marcos, C. F.; Alonso, J. C.; Soler, G.; Centeno, F. Glu-256 is a main structural determinant for oligomerisation of human arginase I. FEBS Lett. 2001, 501 ( 2-3), 161- 165, 10.1016/S0014-5793(01)02650-3
Lobos, M.; Figueroa, M.; Martinez-Oyanedel, J.; Lopez, V.; Garcia-Robles, M. L. A.; Tarifeno-Saldivia, E.; Carvajal, N.; Uribe, E. Insights on the participation of Glu256 and Asp204 in the oligomeric structure and cooperative effects of human arginase type I. J. Struct Biol. 2020, 211 ( 2), 107533 10.1016/j.jsb.2020.107533
Lavulo, L. T.; Sossong, T. M., Jr.; Brigham-Burke, M. R.; Doyle, M. L.; Cox, J. D.; Christianson, D. W.; Ash, D. E. Subunit-subunit interactions in trimeric arginase. Generation of active monomers by mutation of a single amino acid. J. Biol. Chem. 2001, 276 ( 17), 14242- 14248, 10.1074/jbc.M010575200
Carvalho, D. R.; Brand, G. D.; Brum, J. M.; Takata, R. I.; Speck-Martins, C. E.; Pratesi, R. Analysis of novel ARG1 mutations causing hyperargininemia and correlation with arginase I activity in erythrocytes. Gene 2012, 509 ( 1), 124- 130, 10.1016/j.gene.2012.08.003
Grody, W. W.; Klein, D.; Dodson, A. E.; Kern, R. M.; Wissmann, P. B.; Goodman, B. K.; Bassand, P.; Marescau, B.; Kang, S. S.; Leonard, J. V. Molecular genetic study of human arginase deficiency. Am. J. Hum. Genet. 1992, 50 ( 6), 1281- 1290
Scholl-Bürgi, S.; Baumgartner Sigl, S.; Häberle, J.; Haberlandt, E.; Rostásy, K.; Ertl, C.; Eichinger-Öttl, U.; Heinz-Erian, P.; Karall, D. Amino acids in CSF and plasma in hyperammonaemic coma due to arginase1 deficiency. J. Inherited Metab. Dis. 2008, 31, 323- 328, 10.1007/s10545-008-0903-0
Lawrence, S. H.; Ramirez, U. D.; Tang, L.; Fazliyez, F.; Kundrat, L.; Markham, G. D.; Jaffe, E. K. Shape shifting leads to small-molecule allosteric drug discovery. Chem. Biol. 2008, 15 ( 6), 586- 596, 10.1016/j.chembiol.2008.04.012
McMillan, K.; Adler, M.; Auld, D. S.; Baldwin, J. J.; Blasko, E.; Browne, L. J.; Chelsky, D.; Davey, D.; Dolle, R. E.; Eagen, K. A. Allosteric inhibitors of inducible nitric oxide synthase dimerization discovered via combinatorial chemistry. Proc. Natl. Acad. Sci. U. S. A. 2000, 97 ( 4), 1506- 1511, 10.1073/pnas.97.4.1506
Meng, B.; Wu, D.; Gu, J.; Ouyang, S.; Ding, W.; Liu, Z. J. Structural and functional analyses of human tryptophan 2,3-dioxygenase. Proteins 2014, 82 ( 11), 3210- 3216, 10.1002/prot.24653
Ziebarth, T. D.; Gonzalez-Soltero, R.; Makowska-Grzyska, M. M.; Nunez-Ramirez, R.; Carazo, J. M.; Kaguni, L. S. Dynamic effects of cofactors and DNA on the oligomeric state of human mitochondrial DNA helicase. J. Biol. Chem. 2010, 285 ( 19), 14639- 14647, 10.1074/jbc.M109.099663
Wu, D.; Piszczek, G. Standard protocol for mass photometry experiments. Eur. Biophys J. 2021, 50 ( 3-4), 403- 409, 10.1007/s00249-021-01513-9
Chen, P.; Bornhorst, J.; Aschner, M. Manganese metabolism in humans. Front Biosci (Landmark Ed) 2018, 23 ( 9), 1655- 1679, 10.2741/4665
Slordahl, T. S.; Hov, H.; Holt, R. U.; Baykov, V.; Syversen, T.; Sundan, A.; Waage, A.; Borset, M. Mn2+ regulates myeloma cell adhesion differently than the proadhesive cytokines HGF, IGF-1, and SDF-1alpha. Eur. J. Haematol 2008, 81 ( 6), 437- 447, 10.1111/j.1600-0609.2008.01148.x
Miller, S.; Lesk, A. M.; Janin, J.; Chothia, C. The accessible surface area and stability of oligomeric proteins. Nature 1987, 328 ( 6133), 834- 836, 10.1038/328834a0
Gokhale, R. S.; Agarwalla, S.; Francis, V. S.; Santi, D. V.; Balaram, P. Thermal stabilization of thymidylate synthase by engineering two disulfide bridges across the dimer interface. J. Mol. Biol. 1994, 235 ( 1), 89- 94, 10.1016/S0022-2836(05)80018-X
Thoma, R.; Hennig, M.; Sterner, R.; Kirschner, K. Structure and function of mutationally generated monomers of dimeric phosphoribosylanthranilate isomerase from Thermotoga maritima. Structure 2000, 8 ( 3), 265- 276, 10.1016/S0969-2126(00)00106-4
Lunev, S.; Butzloff, S.; Romero, A. R.; Linzke, M.; Batista, F. A.; Meissner, K. A.; Muller, I. B.; Adawy, A.; Wrenger, C.; Groves, M. R. Oligomeric interfaces as a tool in drug discovery: Specific interference with activity of malate dehydrogenase of Plasmodium falciparum in vitro. PLoS One 2018, 13 ( 4), e0195011 10.1371/journal.pone.0195011
Seetoh, W. G.; Abell, C. Disrupting the Constitutive, Homodimeric Protein-Protein Interface in CK2beta Using a Biophysical Fragment-Based Approach. J. Am. Chem. Soc. 2016, 138 ( 43), 14303- 14311, 10.1021/jacs.6b07440
Takahashi, K. Further studies on the reactions of phenylglyoxal and related reagents with proteins. J. Biochem 1977, 81 ( 2), 403- 414, 10.1093/oxfordjournals.jbchem.a131472
Oya, T.; Hattori, N.; Mizuno, Y.; Miyata, S.; Maeda, S.; Osawa, T.; Uchida, K. Methylglyoxal modification of protein. Chemical and immunochemical characterization of methylglyoxal-arginine adducts. J. Biol. Chem. 1999, 274 ( 26), 18492- 18502, 10.1074/jbc.274.26.18492
Patthy, L.; Smith, E. L. Reversible modification of arginine residues. Application to sequence studies by restriction of tryptic hydrolysis to lysine residues. J. Biol. Chem. 1975, 250 ( 2), 557- 564, 10.1016/S0021-9258(19)41933-9
Yankeelov, J. A., Jr.; Mitchell, C. D.; Crawford, T. H. A simple trimerization of 2,3-butanedione yielding a selective reagent for the modification of arginine in proteins. J. Am. Chem. Soc. 1968, 90 ( 6), 1664- 1666, 10.1021/ja01008a056
Riordan, J. F. Arginyl residues and anion binding sites in proteins. Mol. Cell. Biochem. 1979, 26 ( 2), 71- 92, 10.1007/BF00232886
Grzybowski, M. M.; Stanczak, P. S.; Pomper, P.; Blaszczyk, R.; Borek, B.; Gzik, A.; Nowicka, J.; Jedrzejczak, K.; Brzezinska, J.; Rejczak, T. OATD-02 Validates the Benefits of Pharmacological Inhibition of Arginase 1 and 2 in Cancer. Cancers 2022, 14 ( 16), 3967, 10.3390/cancers14163967
Dunand-Sauthier, I.; Irla, M.; Carnesecchi, S.; Seguin-Estevez, Q.; Vejnar, C. E.; Zdobnov, E. M.; Santiago-Raber, M. L.; Reith, W. Repression of arginase-2 expression in dendritic cells by microRNA-155 is critical for promoting T cell proliferation. J. Immunol 2014, 193 ( 4), 1690- 1700, 10.4049/jimmunol.1301913
Kepka-Lenhart, D.; Ash, D. E.; Morris, S. M. Determination of mammalian arginase activity. Methods Enzymol 2008, 440 ( 07), 221- 230, 10.1016/S0076-6879(07)00813-0
Young, G.; Hundt, N.; Cole, D.; Fineberg, A.; Andrecka, J.; Tyler, A.; Olerinyova, A.; Ansari, A.; Marklund, E. G.; Collier, M. P. Quantitative mass imaging of single biological macromolecules. Science 2018, 360 ( 6387), 423- 427, 10.1126/science.aar5839
Nys, G.; Cobraiville, G.; Fillet, M. Multidimensional performance assessment of micro pillar array column chromatography combined to ion mobility-mass spectrometry for proteome research. Anal. Chim. Acta 2019, 1086, 1- 13, 10.1016/j.aca.2019.08.068
