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Evaluation of the use of analogs of crotamine for diagnosis or therapy


Venom toxins are of utmost scientific interest, not only for the studies of the pathophysiological pathways underlying the envenomation processes, but also mainly because of their possible use for therapeutic purposes, i.e. as drug and/or as structural template model for drug development that could be employed for the treatment of human diseases.Considering the biochemical and structural similarities observed between crotamine, which is a toxin from rattlesnake, and the cell penetrating peptides (CPPs), our group has focused the efforts to demonstrate that crotamine is also able to penetrate cells with particular specificity for actively proliferating cells, both in vitro and in vivo. Furthermore, we have also demonstrated that crotamine is capable of carrying DNA molecules into cells with no loss of specificity. More recently, we also demonstrated that the cytotoxic activity of crotamine is selective for cells with high rate of cell division, and this affinity for tumor tissue, as well as its ability to inhibit tumor growth, have both been proven in vivo. This all stimulated us to protect the commercial and industrial use of this compound by filing a patent [INPI No. 05/01037-3 and PCT/BR2006/000052]. The potential application of this peptide as a vector for transfection of mammalian cells has been licensed and currently is operated in conjunction with the Irish company Celtic Biotech.However, the potential possibility of commercial employment of crotamine might be hampered by the limitation of the access to the native crotamine, and this encouraged us to propose studies aiming to evaluate the feasibility of the use of synthetic analogues (full length and/or shorter peptide fragments) and/or recombinant crotamine as an alternative sources of this compound. The potentially use as antimicrobial, antitumour, biomarker and/or as a vector for gene delivery in therapy in vitro and/or in vivo mainly justify the present project. (AU)

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Scientific publications (15)
(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)
CAMPEIRO, JOANA DARC; DAM, WENDY; MONTE, GABRIELA GUILHERME; PORTAL, LUCAS CARVALHO; GONCALVES DE OLIVEIRA, LILIAN CAROLINE; NERING, MARCELA BEGO; VIANA, GUSTAVO MONTEIRO; CARAPETOS, FERNANDO CINTRA; OLIVEIRA, EDUARDO BRANDT; VAN DEN BORN, JACOB; et al. Long term safety of targeted internalization of cell penetrating peptide crotamine into renal proximal tubular epithelial cells in vivo. SCIENTIFIC REPORTS, v. 9, . (13/13392-4, 17/02413-1)
PORTA, LUCAS C.; CAMPEIRO, JOANA D.; PAPA, GIOVANNA B.; OLIVEIRA, EDUARDO B.; GODINHO, ROSELY O.; RODRIGUES, TIAGO; HAYASHI, MIRIAN A. F.. In vivo effects of the association of the psychoactive phenotiazine thioridazine on antitumor activity and hind limb paralysis induced by the native polypeptide crotamine. Toxicon, v. 185, p. 64-71, . (13/13392-4, 18/03102-2, 17/02413-1, 18/00014-5, 18/21381-6)
MONTE, GABRIELA GUILHERME; NANI, V, JOAO; DE ALMEIDA CAMPOS, MARINA ROSSETO; DAL MAS, CAROLINE; NEGRI MARINS, LUCAS AUGUSTO; MARTINS, LUCAS GELAIN; TASIC, LJUBICA; MORI, MARCELO A.; HAYASHI, MIRIAN A. F.. Impact of nuclear distribution element genes in the typical and atypical antipsychotics effects on nematode Caenorhabditis elegans: Putative animal model for studying the pathways correlated to schizophrenia. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 92, p. 19-30, . (14/50867-3, 15/07019-4, 13/13392-4, 17/02413-1, 18/06510-4)
NANI, JOAO V.; LEE, RICHARD S.; YONAMINE, CAMILA M.; SANT'ANNA, OSVALDO A.; JULIANO, MARIA A.; GADELHA, ARY; MARI, JAIR J.; HAYASHI, MIRIAN A. F.. Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics. SCIENTIFIC REPORTS, v. 10, n. 1, . (19/09207-3, 17/02413-1, 12/50191-4, 13/13392-4)
DAL MAS, CAROLINE; ROSSATO, LUANA; SHIMIZU, THAIS; OLIVEIRA, EDUARDO B.; DA SILVA JUNIOR, I, PEDRO; MEIS, JACQUES F.; COLOMBO, ARNALDO LOPES; HAYASHI, MIRIAN A. F.. Effects of the Natural Peptide Crotamine from a South American Rattlesnake on Candida auris, an Emergent Multidrug Antifungal Resistant Human Pathogen. BIOMOLECULES, v. 9, n. 6, . (13/13392-4, 17/02413-1)
CAMPEIRO, JOANA D.; MARINOVIC, MARCELO P.; CARAPETO, FERNANDO CINTRA; DAL MAS, CAROLINE; MONTE, GABRIELA GUILHERME; PORTA, LUCAS CARVALHO; NERING, MARCELA B.; OLIVEIRA, EDUARDO B.; HAYASHI, MIRIAN A. F.. Oral treatment with a rattlesnake native polypeptide crotamine efficiently inhibits the tumor growth with no potential toxicity for the host animal and with suggestive positive effects on animal metabolic profile. Amino Acids, v. 50, n. 2, p. 267-278, . (15/08812-0, 13/13392-4, 17/02413-1)
MARINOVIC, MARCELO P.; CAMPEIRO, JOANA D.; LIMA, SUNAMITA C.; ROCHA, ANDREA L.; NERING, MARCELA B.; OLIVEIRA, EDUARDO B.; MORI, MARCELO A.; HAYASHI, MIRIAN A. F.. Crotamine induces browning of adipose tissue and increases energy expenditure in mice. SCIENTIFIC REPORTS, v. 8, . (13/13392-4, 17/02413-1)
GADELHA, A.; VENDRAMINI, A. M.; YONAMINE, C. M.; NERING, M.; BERBERIAN, A.; SUIAMA, M. A.; OLIVEIRA, V.; LIMA-LANDMAN, M. T.; BREEN, G.; BRESSAN, R. A.; et al. Convergent evidences from human and animal studies implicate angiotensin I-converting enzyme activity in cognitive performance in schizophrenia. TRANSLATIONAL PSYCHIATRY, v. 5, . (13/13392-4, 11/50740-5)
LIMA, SUNAMITA DE CARVALHO; PORTA, LUCAS DE CARVALHO; LIMA, ALVARO DA COSTA; CAMPEIRO, JOANA D'ARC; MEURER, YWLLIANE; TEIXEIRA, NATHALIA BERNARDES; DUARTE, THIAGO; OLIVEIRA, EDUARDO BRANDT; PICOLO, GISELE; GODINHO, ROSELY OLIVEIRA; et al. Pharmacological characterization of crotamine effects on mice hind limb paralysis employing both ex vivo and in vivo assays: Insights into the involvement of voltage-gated ion channels in the crotamine action on skeletal muscles. PLoS Neglected Tropical Diseases, v. 12, n. 8, . (13/13392-4, 15/07019-4, 17/02413-1)
DAL MAS, CAROLINE; NANI, JOAO V.; NOTO, CRISTIANO; YONAMINE, CAMILA M.; DA CUNHA, GRACCIELLE RODRIGUES; MANSUR, RODRIGO B.; OTA, VANESSA K.; BELANGERO, SINTIA IOLE; CORDEIRO, QUIRINO; KAPCZINSKI, FLAVIO; et al. Ndel1 oligopeptidase activity as a potential biomarker of early stages of schizophrenia. SCHIZOPHRENIA RESEARCH, v. 208, p. 202-208, . (13/13392-4, 12/08941-6, 11/50740-5)
TASIC, LJUBICA; PONTES, JOAO G. M.; CARVALHO, MICHELLE S.; CRUZ, GUILHERME; DAL MAS, CAROLINES; SETHI, SUMIT; PEDRINI, MARIANA; RIZZO, LUCAS B.; ZENI-GRAIFF, MAIARA; ASEVEDO, ELSON; et al. Metabolomics and lipidomics analyses by H-1 nuclear magnetic resonance of schizophrenia patient serum reveal potential peripheral biomarkers for diagnosis. SCHIZOPHRENIA RESEARCH, v. 185, p. 182-189, . (13/13392-4, 14/18938-8)
DAL MAS, C.; PINHEIRO, D. A.; CAMPEIRO, J. D.; MATTEI, B.; OLIVEIRA, V.; OLIVEIRA, E. B.; MIRANDA, A.; PEREZ, K. R.; HAYASHI, M. A. F.. Biophysical and biological properties of small linear peptides derived from crotamine, a cationic antimicrobial/antitumoral toxin with cell penetrating and cargo delivery abilities. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, v. 1859, n. 12, p. 2340-2349, . (13/13392-4, 17/02413-1)
GADELHA, ARY; COLEMAN, JONATHAN; BREEN, GEROME; MAZZOTI, DIEGO ROBLES; YONAMINE, CAMILA M.; PELLEGRINO, RENATA; OTA, VANESSA KIYOMI; BELANGERO, SINTIA IOLE; GLESSNER, JOSEPH; SLEIMAN, PATRICK; et al. Genome-wide investigation of schizophrenia associated plasma Ndel1 enzyme activity. SCHIZOPHRENIA RESEARCH, v. 172, n. 1-3, p. 60-67, . (13/13392-4, 12/08941-6, 11/50740-5)
GADELHA, ARY; YONAMINE, CAMILA M.; NERING, MARCELA; RIZZO, LUCAS BORTOLOTTO; NOTO, CRISTIANO; COGO-MOREIRA, HUGO; TEIXEIRA, ANTONIO LUCIO; BRESSAN, RODRIGO; MAES, MICHAEL; BRIETZKE, ELISA; et al. Angiotensin converting enzyme activity is positively associated with IL-17a levels in patients with schizophrenia. PSYCHIATRY RESEARCH, v. 229, n. 3, p. 702-707, . (09/17726-9, 13/13392-4, 11/50740-5)

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Filed patent(s) as a result of this research project

USO DA CROTAMINA PARA A MODULAÇÃO DO METABOLISMO E CONTROLE DE GANHO DE PESO ANIMAL BR1020170009777 - Universidade Federal de São Paulo (UNIFESP) . Mirian Akemi Furuie Hayashi ; Joana D´Arc Campeiro ; Marcelo Paradiso Marinovic ; Marcelo Alves Da Silva Mori - January 2017, 17