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
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):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 about the research grant
Substances associated with bee ferocity are discovered 

Scientific publications (4)
(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)
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: 0.
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: 0.
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: 0.
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: 5.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.
Distribution map of accesses to this page
Click here to view the access summary to this page.