Advanced search
Start date
Betweenand

Natural proteopeptides from the Brazilian fauna, flora and microbiota as potential models for the rational development of new drugs of therapeutic use: isolation, structure elucidation, chemical synthesis and functional activity assays

Grant number: 16/16212-5
Support type:BIOTA-FAPESP Program - Thematic Grants
Duration: June 01, 2017 - May 31, 2022
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Organic Chemistry
Principal Investigator:Mario Sergio Palma
Grantee:Mario Sergio Palma
Home Institution: Instituto de Biociências (IB). Universidade Estadual Paulista (UNESP). Campus de Rio Claro. Rio Claro , SP, Brazil
Assoc. researchers:Ana Marisa Fusco Almeida ; Maria José Soares Mendes Giannini ; Vanderlan da Silva Bolzani
Associated scholarship(s):19/26550-3 - Cyclic peptides from brazilian plants: isolation, structural characterization, synthesis, and evaluation of biological activities, BP.PD
17/06658-9 - Platform for antifungal development in a nanostructured lipid system aiming at efficacy and safety in alternative animal models, BP.PD
17/22405-3 - Identification and Synthesis of peptides corresponding to B-cell linear epitopes in allergens from venom of social Hymenoptera: development of supplies for diagnosis and immunotherapy of allergy, BP.PD

Abstract

Nature offers us an impressive number of different types of biologically active peptides. In multicellular organisms there is a large number of different types of peptides with cell signaling functions, physiological regulation, immune defense, regulation of growth, homeostasis, reproduction, neurotoxicity, production of pain/analgesia, inflammation, among other functions this sense, animal poisons offer many examples of toxins from snakes, scorpions, spiders, insects and marine organisms. The natural peptide toxins inspired the development of drugs for the treatment of chronic pain. Plants have provided important structural models for developing new anti-cancer drugs, and the microorganisms have provided inspiration for the development of several lines of antibiotics. Thus, the objective of this study is to develop a bioprospective work with some specimens of venomous arthropod from Brazilian fauna, with some plants from the flora of Brazilian savanna, and with some microorganisms from Brazilian microbiota, aiming the identification of proteopeptide components presenting novel chemical structures, and interesting functional activities, that could be used as models for the rational development of new drugs for therapeutic use. For these purposes, the detection and isolation approaches will be performed using different types of liquid chromatography, high performance and LC-MS and MS/MS (or MSn) systems. The identified components will have their chemical structures assigned by using a variety of spectroscopic techniques such as spectroscopy, high resolution mass spectrometry, circular dichroism spectroscopy NMR analysis (technical two-dimensional total correlation spectroscopy) to determine the tertiary structure (for some peptides) and/or secondary structure (for other peptides), molecular modeling and molecular dynamics simulations. The peptides will be synthesized in solid phase (combining a series of different experimental strategies) using automated/robotic synthesis system. The Structural Biology Laboratory and Zooquímica the CEIS/IBRC-UNESP is fitted to perform these tasks, and has expertise to develop multiple processes of synthesis in solid phase for linear, cyclic peptides, bridged disulfide bonds (intra and/or extramolecular), and peptides having chemical modifications of the chains sides for different amino acid residues. Synthetic peptides (reproducing natural peptides) will then be purified and subjected to a series of biological activity assays (mast cell degranulation, chemotaxis, antibiosis, inhibition of biofilm formation, inhibition activity of the enzymes COX-1 and COX-2, and anti-mitogenic activity, and toxicity against insect and fish models). All of these bioassays will be conducted with the use of cell cultures, recombinant proteins, and alternative animal models; no mammal will be used. (AU)

Articles published in Agência FAPESP Newsletter about the research grant
Substances associated with bee ferocity are discovered 
Articles published in other media outlets (2 total):
How probiotic Bifidobacteria could help celiac disease patients 
How probiotic Bifidobacteria could help celiac disease patients 

Scientific publications (12)
(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)
JAKOB, THILO; RAUBER, MICHELE MYRIAM; PEREZ-RIVEROL, AMILCAR; SPILLNER, EDZARD; BLANK, SIMON. The Honeybee Venom Major Allergen Api m 10 (Icarapin) and Its Role in Diagnostics and Treatment of Hymenoptera Venom Allergy. CURRENT ALLERGY AND ASTHMA REPORTS, v. 20, n. 9 JUN 16 2020. Web of Science Citations: 0.
MARTINS, DANUBIA BATISTA; PACCA, CAROLINA COLOMBELLI; DA SILVA, ANNIELLE MENDES BRITO; DE SOUZA, BIBIANA MONSON; DE ALMEIDA, MARGARETE TERESA GOTTARDO; PALMA, MARIO SERGIO; ARCISIO-MIRANDA, MANOEL; DOS SANTOS CABRERA, MARCIA PEREZ. Comparing activity, toxicity and model membrane interactions of Jelleine-I and Trp/Arg analogs: analysis of peptide aggregation. Amino Acids, v. 52, n. 5 MAY 2020. Web of Science Citations: 0.
CASTILHO DE ALMEIDA, NATALIA ELLEN; ESTEVES, FRANCIELE GREGO; APARECIDO DOS SANTOS-PINTO, JOSE ROBERTO; DE PAULA, CARLA PERES; DA CUNHA, ANDERSON FERREIRA; MALAVAZI, IRAN; PALMA, MARIO SERGIO; RODRIGUES-FILHO, EDSON. Digestion of Intact Gluten Proteins by Bifidobacterium Species: Reduction of Cytotoxicity and Proinflammatory Responses. Journal of Agricultural and Food Chemistry, v. 68, n. 15, p. 4485-4492, APR 15 2020. Web of Science Citations: 0.
COSTA-LEONARDO, ANA MARIA; DA SILVA, IAGO BUENO; POIANI, SILVANA BEANI; APARECIDO DOS SANTOS-PINTO, JOSE ROBERTO; ESTEVES, FRANCIELE GREGO; BUENO DA SILVA, LUIZA HELENA; PALMA, MARIO SERGIO. Proteomic-components provide insights into the defensive secretion in termite workers of the soldierless genus Ruptitermes. JOURNAL OF PROTEOMICS, v. 213, FEB 20 2020. Web of Science Citations: 0.
PRATAVIEIRA, MARCEL; DA SILVA MENEGASSO, ANALLY RIBEIRO; ROAT, THAISA; MALASPINA, OSMAR; PALMA, MARIO SERGIO. In Situ Metabolomics of the Honeybee Brain: The Metabolism of L-Arginine through the Polyamine Pathway in the Proboscis Extension Response (PER). JOURNAL OF PROTEOME RESEARCH, v. 19, n. 2, p. 832-844, FEB 2020. Web of Science Citations: 0.
SINGULANI, JUNYA DE LACORTE; GALEANE, MARIANA CRISTINA; RAMOS, MARINA DORISSE; GOMES, PAULO CESAR; DOS SANTOS, CLAUDIA TAVARES; DE SOUZA, BIBIANA MONSON; PALMA, MARIO SERGIO; FUSCO ALMEIDA, ANA MARISA; SOARES MENDES GIANNINI, MARIA JOSE. Antifungal Activity, Toxicity, and Membranolytic Action of a Mastoparan Analog Peptide. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 9, DEC 6 2019. Web of Science Citations: 0.
COSTA-LEONARDO, ANA MARIA; DA SILVA, IAGO BUENO; JANEI, VANELIZE; ESTEVES, FRANCIELE GREGO; APARECIDO DOS SANTOS-PINTO, JOSE ROBERTO; PALMA, MARIO SERGIO. Worker Defensive Behavior Associated with Toxins in the Neotropical Termite Neocapritermes braziliensis (Blattaria, Isoptera, Termitidae, Termitinae). Journal of Chemical Ecology, v. 45, n. 9, p. 755-767, SEP 2019. Web of Science Citations: 1.
APARECIDO DOS SANTOS-PINTO, JOSE ROBERTO; ESTEVES, FRANCIELE GREGO; SIALANA, FERNANDO J.; FERRO, MILENE; SMIDAK, ROMAN; RARES, LUCACIU CALIN; NUSSBAUMER, THOMAS; RATTEI, THOMAS; BILBAN, MARTIN; BACCI JUNIOR, MAURICIO; PALMA, MARIO SERGIO; LUEBEC, GERT. A proteotranscriptomic study of silk-producing glands from the orb-weaving spiders. MOLECULAR OMICS, v. 15, n. 4, p. 256-270, AUG 1 2019. Web of Science Citations: 0.
DE SOUZA, CAROLINE LACERRA; APARECIDO DOS SANTOS-PINTO, JOSE ROBERTO; ESTEVES, FRANCIELE GREGO; PEREZ-RIVEROL, AMILCAR; ROMANI FERNANDES, LUIS GUSTAVO; ZOLLNER, RICARDO DE LIMA; PALMA, MARIO SERGIO. Revisiting Polybia paulista wasp venom using shotgun proteomics - Insights into the N-linked glycosylated venom proteins. JOURNAL OF PROTEOMICS, v. 200, p. 60-73, MAY 30 2019. Web of Science Citations: 2.
PEREZ-RIVEROL, AMILCAR; LASA, ALEXIS MUSACCHIO; APARECIDO DOS SANTOS-PINTO, JOSE ROBERTO; PALMA, MARIO SERGIO. Insect venom phospholipases A1 and A2: Roles in the envenoming process and allergy. Insect Biochemistry and Molecular Biology, v. 105, p. 10-24, FEB 2019. Web of Science Citations: 1.
APARECIDO DOS SANTOS-PINTO, JOSE ROBERTO; ARCURI, HELEN ANDRADE; ESTEVES, FRANCIELE GREGO; PALMA, MARIO SERGIO; LUBEC, GERT. Spider silk proteome provides insight into the structural characterization of Nephila clavipes flagelliform spidroin. SCIENTIFIC REPORTS, v. 8, OCT 2 2018. Web of Science Citations: 2.
APARECIDO DOS SANTOS-PINTO, JOSE ROBERTO; PEREZ-RIVEROL, AMILCAR; MUSACCHIO LASA, ALEXIS; PALMA, MARIO SERGIO. Diversity of peptidic and proteinaceous toxins from social Hymenoptera venoms. Toxicon, v. 148, p. 172-196, JUN 15 2018. Web of Science Citations: 7.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.