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Production of extracellular L-asparaginase: from bioprospecting to the engineering of an antileukemic biopharmaceutical

Grant number: 13/08617-7
Support Opportunities:Research Projects - Thematic Grants
Duration: July 01, 2014 - December 31, 2019
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal Investigator:Adalberto Pessoa Junior
Grantee:Adalberto Pessoa Junior
Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Pesquisadores principais:
Gisele Monteiro ; Marcos Antonio de Oliveira
Associated researchers: Attilio Converti ; Carlota de Oliveira Rangel Yagui ; Cristina Maria de Souza Motta ; João Carlos Monteiro de Carvalho ; Jorge Gonzalo Farias Avendano ; Lara Durães Sette ; Pérola de Oliveira e Magalhães ; Priscila Gava Mazzola ; Sandra Helena Poliselli Farsky
Associated grant(s):15/02482-8 - Multi-User Equipment related to grant 201308617-7 - HPLC coupled with mass spectrometry, AP.EMU
14/50237-0 - Production and purification of recombinant proteins of pharmaceutical interest, AP.R
Associated scholarship(s):18/25994-2 - Development of novel platforms for PEGylation of proteins with therapeutic potential using microfluidics, BP.PD
18/24926-3 - L-asparaginase production by recombinant Escherichia coli in high cell density cultivation for a pharmaceutical application, BP.DR
18/25133-7 - Production and characterization of lyposomes and polymersomes for encapsulation of L-asparaginase, BP.IC
 + associated scholarships 17/20384-9 - Development of downstream process of humanized L-asparaginase and its characterization, BP.DR
18/15041-8 - Expression of L-asparaginase from Erwinia chrysanthemi in cell-free protein synthesis technology, BP.MS
17/25272-4 - Asparaginase 1 from Saccharomyces cerevisiae: investigation of the functional and structural effects of the N-terminal domain, BP.IC
18/03734-9 - Implementation of Quality by Design to the Development of the Production Process of the Chemotherapeutical Enzyme L- Asparaginase, BP.PD
17/21819-9 - Optimization and economic feasibility study of recombinant L-asparaginase production process for pharmaceutical application, BP.PD
17/27230-7 - Heterologous expression and functional and structural characterization of asparaginase RmASP1 of Rhodotorula mucilaginosa, BP.IC
17/25065-9 - Production of L-asparaginase by Pichia pastoris in fed-batch bioreactors, BP.DD
17/12458-2 - Biochemical characteristics and antitumor activity of the recombinant protein L-asparaginase I small, BP.IC
16/25896-5 - Biochemical characterization and cytotoxic evaluation of mutant isoforms of L-Asparaginase II from Dickeya chrysanthemi (Erwinia chrysanthemi), BP.DR
16/19245-1 - Evaluation of bacterial strains to L-asparaginase super expression: an antileukemic enzime from Escherichia coli, BP.IC
16/01869-9 - Therapeutic l-asp for LLA purification employing alternative bioprocess, BP.MS
16/16221-4 - Development of polymersomes permeable to L-asparagine for encapsulation of L-asparaginase, BP.PD
16/15787-4 - Cloning of L-asparaginase from Escherichia coli in a Pichia Pastoris strain with humanized glysosylation, BP.IC
16/09138-3 - Engineering of the signal secretory portion of asparaginase from Saccharomyces cerevisiae for extracellular biopharmaceutical production, BP.IC
15/24463-5 - Characterization of L-asparaginase of Erwinia chysanthemi improved by synthetic evolution of proteins and optimization of production conditions, BP.DD
15/20866-8 - Saccharomyces cerevisiae L-asparaginase 1: rational modifications aiming the modulation of kinectic chatacteristics over different substrates, BP.IC
15/04349-3 - Screening of inhibitory molecules for human peroxiredoxin II, seeking treatment for Acute Lymphoid Leukemia (ALL), BP.MS
14/22039-9 - Functional and structural characterization and rational modification of ASPaseM: a new pharmaceutical for the acute lymphoblastic leukemia treatment?, BP.DD
14/10456-4 - Development and characterization of poly(ethylene glycol) methyl ether-Block-Poly (D,L-Lactide) (PEG-PLA) Polymersomes for the release of recombinant L-asparaginase, BP.DR - associated scholarships

Abstract

There is a strong global tendency to find alternative ways to produce pharmaceutical active principles from biotechnology process. In this scenario, Brazil shows a small expression in both research and production. Worsening the situation, international suppliers of biopharmaceuticals to Brazil are losing interest in the market and discontinuing production, especially those related to onco-hematologic treatment. In this context, this project proposes the union of different scientific and technological skills to achieve a viable industrial process to biotechnologically produce L-asparaginase, a biopharmaceutical broadly used in the treatment of leukemia. This project will approach two main areas: optimization of endogenous and heterologous enzyme production, with bioprospecting groups of fungi from diverse biomes; and the protein rational engineering using L-asparaginase from Saccharomyces cerevisiae as scaffold for comparative studies with the bacterial isoforms currently employed in the therapy. Furthermore, crystallographic structures will be determined to guide the site-directed mutations, and random mutations produced by protein synthetic evolution will be evaluated. To improve stability, bioavailability, toxicity and allergenic aspects, many nanotechnology approaches, such as pegylation and nanoencapsulation in polimersomes, will be investigated. As a result, we expect this project can bring a national biopharmaceutical to the market. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
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Scientific publications (60)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
LOUISE LACALENDOLA TUNDISI; DIEGO DE FREITAS COÊLHO; ALESSANDRA VALÉRIA DE SOUSA FARIA; ADALBERTO PESSOA JUNIOR; ELIAS BASILE TAMBOURGI; LAURA DE OLIVEIRA NASCIMENTO; EDGAR SILVEIRA; PRISCILA GAVA MAZZOLA. Two-Step Purification of L-Asparaginase from Acrylaway® L. Brazilian Journal of Pharmaceutical Sciences, v. 58, . (13/08617-7, 16/01869-9)
DOS SANTOS, NATHALIA VIEIRA; SANTOS-EBINUMA, VALERIA DE CARVALHO; PESSOA JUNIOR, ADALBERTO; BRANDAO PEREIRA, JORGE FERNANDO. Liquid-liquid extraction of biopharmaceuticals from fermented broth: trends and future prospects. JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, v. 93, n. 7, SI, p. 1845-1863, . (14/16424-7, 14/01580-3, 14/19793-3, 13/08617-7, 16/07529-5)
SANTOS, JOAO H. P. M.; FLORES-SANTOS, JUAN C.; MENEGUETTI, GIOVANNA P.; RANGEL-YAGUI, CARLOTA O.; COUTINHO, JOAO A. P.; VITOLO, MICHELE; VENTURA, SONIA P. M.; PESSOA, JR., ADALBERTO. In situ purification of periplasmatic L-asparaginase by aqueous two phase systems with ionic liquids (ILs) as adjuvants. JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, v. 93, n. 7, SI, p. 1871-1880, . (13/08617-7)
DE MOURA, WERNER ALFINITO FEIO; SCHULTZ, LEONARDO; BREYER, CARLOS ALEXANDRE; DE OLIVEIRA, ANA LAURA PIRES; TAIRUM, CARLOS ABRUNHOSA; FERNANDES, GABRIELLA COSTA; TOYAMA, MARCOS HIKARI; PESSOA-JR, ADALBERTO; MONTEIRO, GISELE; DE OLIVEIRA, MARCOS ANTONIO. Functional and structural evaluation of the antileukaemic enzymel-asparaginase II expressed at low temperature by differentEscherichia colistrains. Biotechnology Letters, . (13/08617-7, 17/19942-7, 17/25272-4, 19/04054-4, 14/22039-9, 16/19245-1, 17/20291-0, 11/13500-6)
BIASOTO, HENRIQUE P.; HEBEDA, CRISTINA B.; FARSKY, SANDRA H. P.; PESSOA, ADALBERTO; COSTA-SILVA, TALES A.; MONTEIRO, GISELE. Extracellular expression of Saccharomyces cerevisiae's L-asparaginase II in Pichia pastoris results in novel enzyme with better parameters. PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY, v. N/A, p. 12-pg., . (13/08617-7, 18/15104-0, 16/09138-3, 15/07749-2)
KLEINGESINDS, EDUARDO KREBS; PARIZOTTO, LETICIA DE ALMEIDA; EFFER, BRIAN; MONTEIRO, GISELE; LONG, PAUL F.; ARROYO-BERDUGO, YOANA; BEHRENDS, VOLKER; ESPOSITO, MARIA TERESA; CALLE, YOLANDA; PESSOA-JR, ADALBERTO. Downstream process and evaluation of the concomitant impact of a recombinant glycosylated L-asparaginase on leukemic cancer cells and the bone marrow tumor microenvironment. Process Biochemistry, v. 131, p. 11-pg., . (19/06919-2, 13/08617-7, 15/07749-2, 18/03734-9, 17/25065-9, 17/20384-9, 18/15104-0)
MOGUEL, IGNACIO S.; YAMAKAWA, CELINA K.; BRUMANO, LARISSA P.; PESSOA, ADALBERTO; MUSSATTO, SOLANGE I.. Selection and Optimization of Medium Components for the Efficient Production of L-Asparaginase by Leucosporidium scottii L115-A Psychrotolerant Yeast. FERMENTATION-BASEL, v. 8, n. 8, p. 16-pg., . (13/08617-7, 19/03981-9)
LOPES, ANDRE MORENI; RIBEIRO, ARTUR; DE OLIVEIRA, MARCOS ANTONIO; DE SOUZA-MOTTA, CRISTINA MARIA; MAGALHAES, PEROLA DE OLIVEIRA; FARIAS AVENDANO, JORGE GONZALO; MAZZOLA, PRISCILA GAVA; RANGEL-YAGUI, CARLOTA DE OLIVEIRA. Therapeutic l-asparaginase: upstream, downstream and beyond. CRITICAL REVIEWS IN BIOTECHNOLOGY, v. 37, n. 1, p. 82-99, . (13/08617-7, 13/19486-0)
APOLINARIO, ALEXSANDRA CONCEICAO; FERRARO, RAFAEL BERTELLI; DE OLIVEIRA, CAMILA AREIAS; PESSOA, ADALBERTO, JR.; RANGEL-YAGUI, CARLOTA DE OLIVEIRA. Quality-by-Design Approach for Biological API Encapsulation into Polymersomes Using "Off-the-Shelf" Materials: a Study on L-Asparaginase. AAPS PHARMSCITECH, v. 20, n. 6, p. 12-pg., . (14/10456-4, 16/03887-4, 13/08617-7, 17/03811-0)
SANCHEZ-MOGUEL, IGNACIO; COSTA-SILVA, TALES A.; PILLACA-PULLO, OMAR S.; FLORES-SANTOS, JUAN CARLOS; BARROS FREIRE, ROMINNE KARLA; CARRETERO, GUSTAVO; BUENO, JULIA DA LUZ; CAMACHO-CORDOVA, DAVID I.; SANTOS, JOAO H. P. M.; SETTE, LARA DURAES; et al. Antarctic yeasts as a source of L-asparaginase: Characterization of a glutaminase-activity free L-asparaginase from psychrotolerant yeast Leucosporidium scottii L115. Process Biochemistry, v. 129, p. 12-pg., . (19/23620-0, 13/19584-2, 13/08617-7)
SCHULTZ, L.; MONTEIRO, G.; PESSOA-, A., JR.; DE OLIVEIRA, M. A.. A new L-asparaginase as a promising biodrug to acute lymphoblastic leukemia treatment. Annals of Oncology, v. 27, p. 2-pg., . (13/08617-7)
TUNDISI, LOUISE LACALENDOLA; COELHO, DIEGO DE FREITAS; DE SOUSA FARIA, ALESSANDRA VALERIA; PESSOA JUNIOR, ADALBERTO; TAMBOURGI, ELIAS BASILE; NASCIMENTO, LAURA DE OLIVEIRA; SILVEIRA, EDGAR; MAZZOLA, PRISCILA GAVA. Two-Step Purification of L-Asparaginase from Acrylaway((R)) L. Brazilian Journal of Pharmaceutical Sciences, v. 58, p. 13-pg., . (16/01869-9, 13/08617-7)
ALEXSANDRA CONCEIÇÃO APOLINÁRIO; JULIANA DE ALMEIDA PACHIONI-VASCONCELOS; ADALBERTO PESSOA JR.; CARLOTA DE OLIVEIRA RANGEL-YAGUI. POLIMEROSSOMOS VERSUS LIPOSSOMOS: A EVOLUÇÃO DA “BALA MÁGICA”. Química Nova, v. 40, n. 7, p. 810-817, . (14/10456-4, 13/08617-7)
HERRERA BELEN, LISANDRA; BELTRAN LISSABET, JORGE F.; RANGEL-YAGUI, CARLOTA DE OLIVEIRA; MONTEIRO, GISELE; PESSOA, ADALBERTO; FARIAS, JORGE G.. Immunogenicity assessment of fungal L-asparaginases: an in silico approach. SN APPLIED SCIENCES, v. 2, n. 2, . (13/08617-7)
FLORES-SANTOS, JUAN CARLOS; MOGUEL, IGNACIO S.; MONTEIRO, GISELE; PESSOA, ADALBERTO; VITOLO, MICHELE. Improvement in extracellular secretion of recombinant l-asparaginase II by Escherichia coli BL21 (DE3) using glycine and n-dodecane. Brazilian Journal of Microbiology, v. 52, n. 3, p. 1247-1255, . (13/08617-7)
LIMA, GUILHERME M.; ATRAZHEV, ALEXEY; SARKAR, SUSMITA; SOJITRA, MIRAT; REDDY, REVATHI; TORRES-OBREQUE, KARIN; RANGEL-YAGUI, CARLOTA DE OLIVEIRA; MACAULEY, MATTHEW S.; MONTEIRO, GISELE; DERDA, RATMIR. DNA-Encoded Multivalent Display of Chemically Modified Protein Tetramers on Phage: Synthesis and in Vivo Applications. ACS Chemical Biology, . (13/08617-7, 16/22065-5, 18/15041-8, 19/09354-6, 18/15104-0)
WLODARCZYK, SAMARINA R.; CUSTODIO, DEBORA; PESSOA JR, ADALBERTO; MONTEIRO, GISELE. Influence and effect of osmolytes in biopharmaceutical formulations. EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, v. 131, p. 92-98, . (15/24463-5, 13/08617-7, 13/24024-6, 15/07749-2)
EFFER, BRIAN; LIMA, GUILHERME MEIRA; CABARCA, SINDY; PESSOA, ADALBERTO; FARIAS, JORGE G.; MONTEIRO, GISELE. L-Asparaginase from E. chrysanthemi expressed in glycoswitch: effect of His-Tag fusion on the extracellular expression. PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY, v. 49, n. 7, . (17/20384-9, 16/25896-5, 15/07749-2, 13/08617-7, 16/15787-4)
DANIELA CAMARGO FURUYA; SILGIA APARECIDA DA COSTA; RODRIGO CARDOSO DE OLIVEIRA; HUMBERTO GOMES FERRAZ; ADALBERTO PESSOA JUNIOR; SIRLENE MARIA DA COSTA. Fibers Obtained from Alginate, Chitosan and Hybrid Used in the Development of Scaffolds. MATERIALS RESEARCH-IBERO-AMERICAN JOURNAL OF MATERIALS, v. 20, n. 2, p. 377-386, . (13/08617-7)
SANTOS, JOAO H. P. M.; COSTA, IRIS M.; MOLINO, JOAO V. D.; LEITE, MARIANA S. M.; PIMENTA, MARCELA V.; COUTINHO, JOAO A. P.; PESSOA, JR., ADALBERTO; VENTURA, SONIA P. M.; LOPES, ANDRE M.; MONTEIRO, GISELE. Heterologous expression and purification of active L-asparaginase I of Saccharomyces cerevisiae in Escherichia coli host. BIOTECHNOLOGY PROGRESS, v. 33, n. 2, p. 416-424, . (15/07749-2, 13/08617-7)
TORRES-OBREQUE, KARIN; MENEGUETTI, GIOVANNA PASTORE; CUSTODIO, DEBORA; MONTEIRO, GISELE; PESSOA-JUNIOR, ADALBERTO; DE OLIVEIRA RANGEL-YAGUI, CARLOTA. Production of a novel N-terminal PEGylated crisantaspase. Biotechnology and Applied Biochemistry, v. 66, n. 3, p. 281-289, . (16/22065-5, 13/08617-7)
COSTA-SILVA, T. A.; CAMACHO-CORDOVA, D. I.; AGAMEZ-MONTALVO, G. S.; PARIZOTTO, L. A.; SANCHEZ-MOGUEL, I.; PESSOA-, JR., A.. Optimization of culture conditions and bench-scale production of anticancer enzyme L-asparaginase by submerged fermentation from Aspergillus terreus CCT 7693. PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY, v. 49, n. 1, p. 95-104, . (13/08617-7, 13/19584-2)
MEDEIROS DE BRITO, ANNA EMMANUELA; PESSOA, JR., ADALBERTO; CONVERTI, ATTILIO; RANGEL-YAGUI, CARLOTA DE OLIVEIRA; DA SILVA, JOSE ALEXSANDRO; APOLINARIO, ALEXSANDRA CONCEICAO. Poly (lactic-co-glycolic acid) nanospheres allow for high L-asparaginase encapsulation yield and activity. Materials Science & Engineering C-Materials for Biological Applications, v. 98, p. 524-534, . (13/08617-7, 14/10456-4, 17/08123-5)
CARDOSO, SAMUEL L.; DE FREITAS, MARCELA M.; DE SOUZA, PAULA M.; HOMEM-DE-MELLO, MAURICIO; SILVEIRA, DAMARIS; FONSECA-BAZZO, YRIS MARIA; FILHO, EDIVALDO X.; JUNIOR, ADALBERTO P.; MAGALHAES, PEROLA O.. Optimization of aqueous two-phase micellar system for partial purification of L-asparaginase from Penicillium sp. grown in wheat bran as agro-industrial residue. Brazilian Journal of Microbiology, v. 51, n. 3, . (13/08617-7)
GUIMARAES, MARINA DE SOUZA; MUSO CACHUMBA, JORGE JAVIER; BUENO, CECILIA ZORZI; TORRES-OBREQUE, KARIN MARIANA; RUIZ LARA, GRACE VERONICA; MONTEIRO, GISELE; SOUZA BARBOSA, LEANDRO RAMOS; PESSOA JR, ADALBERTO; RANGEL-YAGUI, CARLOTA DE OLIVEIRA. Peg-Grafted Liposomes for L-Asparaginase Encapsulation. PHARMACEUTICS, v. 14, n. 9, p. 18-pg., . (18/15104-0, 13/08617-7, 15/15822-1, 14/10456-4)
EFFER, BRIAN; KLEINGESINDS, EDUARDO KREBS; LIMA, GUILHERME MEIRA; COSTA, IRIS MUNHOZ; SANCHEZ-MOGUEL, IGNACIO; PESSOA, ADALBERTO; SANTIAGO, VERONICA FEIJOLI; PALMISANO, GIUSEPPE; FARIAS, JORGE G.; MONTEIRO, GISELE. Glycosylation of Erwinase results in active protein less recognized by antibodies. Biochemical Engineering Journal, v. 163, p. 11-pg., . (13/08617-7, 15/07749-2, 17/20384-9, 18/15104-0, 16/15787-4, 16/25896-5)
SANTOS-EBINUMA, VALERIA CARVALHO; LOPES, ANDRE MORENI; PESSOA, JR., ADALBERTO; SIMAS TEIXEIRA, MARIA FRANCISCA. Extraction of natural red colorants from the fermented broth of Penicillium purpurogenum using aqueous two-phase polymer systems. BIOTECHNOLOGY PROGRESS, v. 31, n. 5, p. 1295-1304, . (13/08617-7)
MAGRI, AGNES; PIMENTA, MARCELA V.; SANTOS, JOAO H. P. M.; COUTINHO, JOAO A. P.; VENTURA, SONIA P. M.; MONTEIRO, GISELE; RANGEL-YAGUI, CARLOTA O.; PEREIRA, JORGE F. B.. Controlling the l-asparaginase extraction and purification by the appropriate selection of polymer/salt-based aqueous biphasic systems. JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, v. 95, n. 4, p. 1016-1027, . (13/08617-7, 18/15104-0, 14/16424-7, 18/25994-2, 14/19793-3, 15/07749-2)
SANTOS, JOAO H. P. M.; MENDONCA, CARLOS M. N.; SILVA, AMANDA R. P.; OLIVEIRA, RICARDO P. S.; PESSOA JR, ADALBERTO; COUTINHO, JOAO A. P.; VENTURA, SONIA P. M.; RANGEL-YAGUI, CARLOTA O.. An integrated process combining the reaction and purification of PEGylated proteins. GREEN CHEMISTRY, v. 21, n. 23, p. 6407-6418, . (16/22065-5, 13/08617-7, 18/25994-2)
APOLINARIO, ALEXSANDRA CONCEICAO; FERRARO, RAFAEL BERTELLI; DE OLIVEIRA, CAMILA AREIAS; PESSOA, JR., ADALBERTO; RANGEL-YAGUI, CARLOTA DE OLIVEIRA. Quality-by-Design Approach for Biological API Encapsulation into Polymersomes Using ``Off-the-Shelf{''} Materials: a Study on L-Asparaginase. AAPS PHARMSCITECH, v. 20, n. 6, . (17/03811-0, 13/08617-7, 16/03887-4, 14/10456-4)
DA SILVA, LEONARDO SCHULTZ; DOONAN, LIAM B.; PESSOA, JR., ADALBERTO; DE OLIVEIRA, MARCOS ANTONIO; LONG, PAUL F.. Structural and functional diversity of asparaginases: Overview and recommendations for a revised nomenclature. Biotechnology and Applied Biochemistry, . (18/04685-1, 13/08617-7, 14/22039-9, 17/19942-7)
LIMA, GUILHERME M.; MENEZES, MILENE C.; COSTA, IRIS M.; SERRANO, SOLANGE M. T.; MONTEIRO, GISELE. Development of a cell-free protein synthesis protocol to rapidly screen L-asparaginase proteoforms by enzymatic activity. JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, . (13/08617-7, 18/15041-8, 16/25896-5, 13/07467-1, 18/15104-0)
FLORES-SANTOS, JUAN CARLOS; MOGUEL, IGNACIO S.; MONTEIRO, GISELE; PESSOA, ADALBERTO; VITOLO, MICHELE. Improvement in extracellular secretion of recombinant l-asparaginase II by Escherichia coli BL21 (DE3) using glycine and n-dodecane. Brazilian Journal of Microbiology, . (13/08617-7)
PILLACA-PULLO, OMAR; RODRIGUES, DAVID; SANCHEZ-MOGUEL, IGNACIO; LOPES, ANDRE; PIMENTA, MARCELA; BASI, TAJINDAR; FEITOSA, VALKER; IRIS ZAVALETA, AMPARO; MONTEIRO, GISELE; PESSOA JR, ADALBERTO; et al. Recombinantl-asparaginase production usingPichia pastoris(MUT(s)strain): establishment of conditions for growth and induction phases. JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, v. 96, n. 1, . (13/08617-7, 17/10789-1)
COSTA, IRIS MUNHOZ; MOURA, DEBORA CUSTODIO; LIMA, GUILHERME MEIRA; PESSOA, ADALBERTO; DOS SANTOS, CAMILA ORESCO; DE OLIVEIRA, MARCOS A.; MONTEIRO, GISELE. Engineered asparaginase from Erwinia chrysanthemi enhances asparagine hydrolase activity and diminishes enzyme immunoreactivity - a new promise to treat acute lymphoblastic leukemia. JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, v. 97, n. 1, . (16/25896-5, 15/07749-2, 18/15104-0, 13/08617-7)
DOS SANTOS, NATHALIA VIEIRA; SANTOS-EBINUMA, VALERIA DE CARVALHO; PESSOA JUNIOR, ADALBERTO; BRANDAO PEREIRA, JORGE FERNANDO. Liquid-liquid extraction of biopharmaceuticals from fermented broth: trends and future prospects. JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, v. 93, n. 7, p. 19-pg., . (14/16424-7, 14/01580-3, 16/07529-5, 13/08617-7, 14/19793-3)
DA SILVA, LEONARDO SCHULTZ; DOONAN, LIAM B.; PESSOA, ADALBERTO, JR.; DE OLIVEIRA, MARCOS ANTONIO; LONG, PAUL F.. Structural and functional diversity of asparaginases: Overview and recommendations for a revised nomenclature. Biotechnology and Applied Biochemistry, v. 69, n. 2, p. 11-pg., . (18/04685-1, 13/08617-7, 17/19942-7, 14/22039-9)
TUNDISI, LOUISE L.; COELHO, DIEGO F.; ZANCHETTA, BEATRIZ; MORIEL, PATRICIA; PESSOA, JR., ADALBERTO; TAMBOURGI, ELIAS B.; SILVEIRA, EDGAR; MAZZOLA, PRISCILA G.. L-Asparaginase Purification. SEPARATION AND PURIFICATION REVIEWS, v. 46, n. 1, p. 35-43, . (13/08617-7)
TORRES-OBREQUE, KARIN; KLEINGESINDS, EDUARDO KREBS; SANTOS, JOAO H. P. M.; CARRETERO, GUSTAVO; RABELO, JHENIFFER; CONVERTI, ATTILIO; MONTEIRO, GISELE; PESSOA JR, ADALBERTO; RANGEL-YAGUI, CARLOTA O.. PEGylation versus glycosylation: effect on the thermodynamics and thermostability of crisantaspase. PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY, v. N/A, p. 11-pg., . (16/22065-5, 17/20384-9, 13/08617-7, 18/25994-2)
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MÉTODO DE OBTENÇÃO DE L-ASPARAGINASE RECOMBINANTE DE BAIXA MASSA MOLAR, L-ASPARAGINASE RECOMBINANTE E USO DA MESMA BR1020160247020 - Universidade de São Paulo (USP) ; Universidade Estadual Paulista (UNESP) . Marcos Antonio de Oliveira ; Gisele Monteiro de Souza ; Adalberto Pessoa Junior ; Leonardo Schultz da Silva ; Iris Munhoz Costa ; Marcos Hiraki Toyama ; Sandra Helena Poliselli Farsky - October 2016, 21

USO DE DITERPENOIDES ENT-CAURÂNOS EM ASSOCIAÇÃO A ANTIBIÓTICOS PARA INIBIÇÃO DE ENZIMAS PEROXIRREDOXINAS DE MICRORGANISMOS PARA O COMBATE DE INFECÇÕES MICROBIANAS BR1020200162454 - Universidade de São Paulo (USP) ; Universidade Estadual Julio de Mesquita Filho (UNESP) . GISELE MONTEIRO / Adalberto Pessoa Junior / ANA JÚLIA FERNANDES CARDOSO DE OLIVEIRA / BRUNA DEL BUSSO ZAMPIERI / CARLOS ABRUNHOSA TAIRUM JUNIOR / CARLOS ALEXANDRE BREYER / LUIS EDUARDO SOARES NETTO / MARCOS ANTONIO DE OLIVEIRA / MARCOS HIKARI TOYAMA / MELINA CARDOSO DOS SANTOS / ROLANDO IÉ / VANESSA DA COSTA ANDRADE - August 2020, 10