Bioactive peptides and peptidases: biological and immunobiological activities in infectious diseases and cancer

• Grant number: 10/51423-0
• Support Opportunities: Research Projects - Thematic Grants
• Start date: January 01, 2011
• End date: December 31, 2016
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Luiz Rodolpho Raja Gabaglia Travassos
• Grantee: Luiz Rodolpho Raja Gabaglia Travassos
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Pesquisadores principais: Adriana Karaoglanovic Carmona ; Elaine Guadelupe Rodrigues
• Associated scholarship(s): 15/11314-1 - Antitumor activity of peptides derived from immunoglobulins exerted in vivo involving dendritic cells and TGF-beta family protein signaling, BP.IC; 11/15562-9 - Expression and function of kinin receptors in tumor cells and in cells of the immune system, BP.MS; 11/14403-4 - Processment of plasmatic proteins by Plasmodium, BP.DR; 11/07685-3 - Bradykinin as an immunomodulator of antitumor immune response, BP.IC; 09/11261-4 - Study of action of proteases of Plasmodium falciparum in the parasite-host relationship, BP.PD

Abstract

Studies on the structure and mechanisms of action of bioactive peptides and peptidases in experimental models of infectious diseases and cancer. All subprojects depend on an active sector of synthesis and analysis of peptides as installed at the Biophysics Department of UNIFESP. Peptides and peptidases are so broadly involved in the functioning of cells and multicellular organisms that virtually all biological or experimental model systems do use substrates, inhibitors, antibiotics, mediators, antigens that are peptides, as well as regulatory enzymes that degrade, generate or chaperone peptides. The different biological activities of peptides and peptidases are always interlinked representing major steps in a variety of key events in biology and medicine. The project involves different lines of investigation comprising the synthesis of peptides and derivatives, and the use of peptide inhibitors in experiments of immune protection, antimicrobial and antitumor cytotoxicity, regulation of the immune response. In the field of peptidases, lines focusing on the characterization of lysosomal cathepsins B, L, and S expressed in murine melanoma B16F10-Nex2 and their involvement in angiogenesis and tumorigenesis; identification of modulators and proteolytic peptides of the kinin-kallikrein system related to tumor angiogenesis; the role of lysosomal cathepsins (V, S, K, L and B) in physiological and pathophysiological processes of the eye; leptin hydrolysis by lysosomal cysteine proteases, and lysosomal cathepsins present in Plasmodium falciparum cell cultures that are active on the hydrolysis of synthetic substrates with sequences corresponding to kinins; kinetic studies of Oligopeptidase A (OpdA) containing targeted site mutations; proteases as a new therapeutic antitumor alternative: use of arazyme as a protective agent in the B16F10-Nex2 murine melanoma model; production and characterization of metacaspases (MCAs): study of programmed cell death in lower eukaryotes; study of the involvement of metallo-peptidase PHEX on physiological and pathophysiological processes. FRET-peptides, inhibitors, and updated analytical methods. (AU)

Scientific publications

(20)

(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)

MELO, POLLYANA M. S.; BAGNARESI, PIERO; PASCHOALIN, THAYSA; HIRATA, IZAURA Y.; GAZARINI, MARCOS L.; CARMONA, ADRIANA K.. Plasmodium falciparum proteases hydrolyze plasminogen, generating angiostatin-like fragments. Molecular and Biochemical Parasitology, v. 193, n. 1, p. 45-54, JAN 2014. (10/51423-0, 09/11261-4, 09/53840-0)

GIROLA, NATALIA; RESENDE-LARA, PEDRO T.; FIGUEIREDO, CARLOS R.; MASSAOKA, MARIANA H.; AZEVEDO, RICARDO A.; CUNHA, RODRIGO L. O. R.; POLONELLI, LUCIANO; TRAVASSOS, LUIZ R.. Molecular, Biological and Structural Features of V-L CDR-1 Rb44 Peptide, Which Targets the Microtubule Network in Melanoma Cells. FRONTIERS IN ONCOLOGY, v. 9, JAN 25 2019. (10/51423-0)

MASSAOKA, MARIANA H.; MATSUO, ALISSON L.; FIGUEIREDO, CARLOS R.; GIROLA, NATALIA; FARIA, CAMYLA F.; AZEVEDO, RICARDO A.; TRAVASSOS, LUIZ R.. A novel cell-penetrating peptide derived from WT1 enhances p53 activity, induces cell senescence and displays antimelanoma activity in xeno- and syngeneic systems. FEBS OPEN BIO, v. 4, p. 153-161, 2014. (12/19476-2, 10/51423-0)

FIGUEIREDO, CARLOS R.; MATSUO, ALISSON L.; AZEVEDO, RICARDO A.; MASSAOKA, MARIANA H.; GIROLA, NATALIA; POLONELLI, LUCIANO; TRAVASSOS, LUIZ R.. A novel microtubule de-stabilizing complementarity-determining region C36L1 peptide displays antitumor activity against melanoma in vitro and in vivo. SCIENTIFIC REPORTS, v. 5, SEP 22 2015. (10/51423-0)

MUNOZ, JULIAN E.; LUFT, VINICIUS D.; AMORIM, JULIANA; MAGALHES, ADRIANA; THOMAZ, LUCIANA; NOSANCHUK, JOSHUA D.; TRAVASSOS, LUIZ R.; TABORDA, CARLOS P.. Immunization with P10 Peptide Increases Specific Immunity and Protects Immunosuppressed BALB/c Mice Infected with Virulent Yeasts of Paracoccidioides brasiliensis. Mycopathologia, v. 178, n. 3-4, p. 177-188, OCT 2014. (11/17267-4, 10/51423-0)

MASSAOKA, MARIANA H.; MATSUO, ALISSON L.; FIGUEIREDO, CARLOS R.; FARIAS, CAMYLA F.; GIROLA, NATALIA; ARRUDA, DENISE C.; SCUTTI, JORGE A. B.; ROMOFF, PAULETE; FAVERO, ORIANA A.; FERREIRA, MARCELO J. P.; et al. Jacaranone Induces Apoptosis in Melanoma Cells via ROS-Mediated Downregulation of Akt and p38 MAPK Activation and Displays Antitumor Activity In Vivo. PLoS One, v. 7, n. 6, p. e38698, 2012. (10/51423-0)

PEREIRA, FELIPE V.; FERREIRA-GUIMARAES, CARLA A.; PASCHOALIN, THAYSA; SCUTTI, JORGE A. B.; MELO, FILIPE M.; SILVA, LUIS S.; MELO, AMANDA C. L.; SILVA, PRISCILA; TIAGO, MANOELA; MATSUO, ALISSON L.; et al. A Natural Bacterial-Derived Product, the Metalloprotease Arazyme, Inhibits Metastatic Murine Melanoma by Inducing MMP-8 Cross-Reactive Antibodies. PLoS One, v. 9, n. 4, APR 30 2014. (12/50191-4, 10/51423-0)

ARRUDA, DENISE COSTA; DE OLIVEIRA, THAIS DOLZANY; FUKUDA CURSINO, PATRICIA HARUME; CARNEIRO MAIA, VERA SUSANA; BERZAGHI, RODRIGO; TRAVASSOS, LUIZ R.; TADA, DAYANE BATISTA. Inhibition of melanoma metastasis by dual-peptlde PLGA NPS. Biopolymers, v. 108, n. 5, SEP 2017. (11/23895-8, 15/05980-9, 10/51423-0)

MAIA, VERA S. C.; BERZAGHI, RODRIGO; ARRUDA, DENISE C.; MACHADO, FABRICIO C.; LOUREIRO, LETICIA L.; MELO, POLLYANA M. S.; MORAIS, ALICE S.; BUDU, ALEXANDRE; TRAVASSOS, LUIZ R.. PLP2-derived peptide Rb4 triggers PARP-1-mediated necrotic death in murine melanoma cells. SCIENTIFIC REPORTS, v. 12, n. 1, p. 13-pg., 2022-02-21. (10/51423-0)

MACHADO, FABRICIO C.; GIROLA, NATALIA; MAIA, VERA S. C.; BERGAMI-SANTOS, PATRICIA C.; MORAIS, ALICE S.; AZEVEDO, RICARDO A.; FIGUEIREDO, CARLOS R.; BARBUTO, JOSE A. M.; TRAVASSOS, LUIZ R.. Immunomodulatory Protective Effects of Rb9 Cyclic-Peptide in a Metastatic Melanoma Setting and the Involvement of Dendritic Cells. FRONTIERS IN IMMUNOLOGY, v. 10, JAN 15 2020. (10/51423-0, 09/54599-5)

TRAVASSOS, LUIZ R.; TABORDA, CARLOS P.. Linear epitopes of Paracoccidioides brasiliensis and Other Fungal Agents of Human Systemic Mycoses As vaccine Candidates. FRONTIERS IN IMMUNOLOGY, v. 8, MAR 10 2017. (10/51423-0, 16/08730-6)

GIROLA, NATALIA; MATSUO, ALISSON L.; FIGUEIREDO, CARLOS R.; MASSAOKA, MARIANA H.; FARIAS, CAMYLA F.; ARRUDA, DENISE C.; AZEVEDO, RICARDO A.; MONTEIRO, HUGO P.; RESENDE-LARA, PEDRO T.; CUNHA, RODRIGO L. O. R.; et al. The Ig V-H complementarity-determining region 3-containing Rb9 peptide, inhibits melanoma cells migration and invasion by interactions with Hsp90 and an adhesion G-protein coupled receptor. Peptides, v. 85, p. 1-15, NOV 2016. (10/51423-0)

BERZAGHI, R.; MAIA, V. S. C.; PEREIRA, F. V.; MELO, F. M.; GUEDES, M. S.; ORIGASSA, C. S. T.; SCUTTI, J. B.; MATSUO, A. L.; CAMARA, N. O. S.; RODRIGUES, E. G.; et al. SOCS1 favors the epithelial-mesenchymal transition in melanoma, promotes tumor progression and prevents antitumor immunity by PD-L1 expression. SCIENTIFIC REPORTS, v. 7, JAN 12 2017. (10/51423-0)

MASSAOKA, MARIANA H.; MATSUO, ALISSON L.; FIGUEIREDO, CARLOS R.; GIROLA, NATALIA; FARIAS, CAMYLA F.; PASQUALOTO, KERLY; TRAVASSOS, LUIZ R.. A subtraction tolerization method of immunization allowed for Wilms' tumor protein-1 (WT1) identification in melanoma and discovery of an antitumor peptide sequence. JOURNAL OF IMMUNOLOGICAL METHODS, v. 414, p. 11-19, DEC 1 2014. (10/51423-0)

FIGUEIREDO, CARLOS R.; MATSUO, ALISSON L.; MASSAOKA, MARIANA H.; POLONELLI, LUCIANO; TRAVASSOS, LUIZ R.. Anti-tumor activities of peptides corresponding to conserved complementary determining regions from different immunoglobulins. Peptides, v. 59, p. 14-19, SEP 2014. (10/51423-0)

DE AMORIM, JULIANA; MAGALHAES, ADRIANA; MUNOZ, JULIAN ESTEBAN; RITTNER, GLAUCE M. G.; NOSANCHUK, JOSHUA D.; TRAVASSOS, LUIZ R.; TABORDA, CARLOS P.. DNA vaccine encoding peptide P10 against experimental paracoccidioidomycosis induces long-term protection in presence of regulatory T cells. Microbes and Infection, v. 15, n. 3, p. 181-191, MAR 2013. (11/17267-4, 09/15823-7, 10/51423-0)

MAGALHAES, A.; FERREIRA, K. S.; ALMEIDA, S. R.; NOSANCHUK, J. D.; TRAVASSOS, L. R.; TABORDA, C. P.. Prophylactic and Therapeutic Vaccination Using Dendritic Cells Primed with Peptide 10 Derived from the 43-Kilodalton Glycoprotein of Paracoccidioides brasiliensis. Clinical and Vaccine Immunology, v. 19, n. 1, p. 23-29, JAN 2012. (09/15823-7, 10/51423-0)

ARRUDA, DENISE C.; SANTOS, LUANA C. P.; MELO, FILIPE M.; PEREIRA, FELIPE V.; FIGUEIREDO, CARLOS R.; MATSUO, ALISSON L.; MORTARA, RENATO A.; JULIANO, MARIA A.; RODRIGUES, ELAINE G.; DOBROFF, ANDREY S.; et al. beta-Actin-binding Complementarity-determining Region 2 of Variable Heavy Chain from Monoclonal Antibody C7 Induces Apoptosis in Several Human Tumor Cells and Is Protective against Metastatic Melanoma. Journal of Biological Chemistry, v. 287, n. 18, p. 14912-14922, APR 27 2012. (06/50634-2, 10/51423-0)

TRAVASSOS, LUIZ R.; TABORDA, CARLOS P.. Paracoccidioidomycosis vaccine. HUMAN VACCINES & IMMUNOTHERAPEUTICS, v. 8, n. 10, p. 1450-1453, OCT 2012. (10/51423-0)

DE OLIVEIRA, THAIS DOLZANY; TRAVASSOS, LUIZ R.; ARRUDA, DENISE COSTA; TADA, DAYANE BATISTA. Intracellular Targeting of Poly Lactic-Co-Glycolic Acid Nanoparticles by Surface Functionalization with Peptides. JOURNAL OF BIOMEDICAL NANOTECHNOLOGY, v. 17, n. 7, p. 1320-1329, JUL 2021. (11/23895-8, 15/05980-9, 17/01697-6, 18/11972-7, 10/51423-0)