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Antioxidant and Neuroprotective Effects of the First Tryptophyllin Found in Snake Venom (Bothrops moojeni)
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    Antioxidant and Neuroprotective Effects of the First Tryptophyllin Found in Snake Venom (Bothrops moojeni)
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    • Anderson Dematei
      Anderson Dematei
      Center for Tropical Medicine (NMT), Faculty of Medicine, University of Brasilia, Brasília 70910-900, Brazil
      Research Center in Morphology and Applied Immunology (NuPMIA), Faculty of Medicine, University of Brasilia, Brasília 70910-900, Brazil
    • Samuel Ribeiro Costa
      Samuel Ribeiro Costa
      Laboratory for the Synthesis and Analysis of Biomolecules (LSAB), Institute of Chemistry, University of Brasilia, Brasília 70910-900, Brazil
    • Daniel C. Moreira
      Daniel C. Moreira
      Research Center in Morphology and Applied Immunology (NuPMIA), Faculty of Medicine, University of Brasilia, Brasília 70910-900, Brazil
    • Eder Alves Barbosa
      Eder Alves Barbosa
      Research Center in Morphology and Applied Immunology (NuPMIA), Faculty of Medicine, University of Brasilia, Brasília 70910-900, Brazil
      Laboratory for the Synthesis and Analysis of Biomolecules (LSAB), Institute of Chemistry, University of Brasilia, Brasília 70910-900, Brazil
    • Lucas F. Friaça Albuquerque
      Lucas F. Friaça Albuquerque
      Research Center in Morphology and Applied Immunology (NuPMIA), Faculty of Medicine, University of Brasilia, Brasília 70910-900, Brazil
    • Andreanne G. Vasconcelos
      Andreanne G. Vasconcelos
      Research Center in Morphology and Applied Immunology (NuPMIA), Faculty of Medicine, University of Brasilia, Brasília 70910-900, Brazil
    • Tiago Nascimento
      Tiago Nascimento
      Research Center on Biodiversity and Biotechnology (Biotec), Parnaiba Delta Federal University, Parnaíba 64202-020, Brazil
    • Pedro Costa Silva
      Pedro Costa Silva
      Research Center on Biodiversity and Biotechnology (Biotec), Parnaiba Delta Federal University, Parnaíba 64202-020, Brazil
    • Amandda É. Silva-Carvalho
      Amandda É. Silva-Carvalho
      Laboratory of Hematology and Stem Cells (LHCT), Faculty of Health Sciences, University of Brasília, Brasília 70910-900, Brazil
    • Felipe Saldanha-Araújo
      Felipe Saldanha-Araújo
      Laboratory of Hematology and Stem Cells (LHCT), Faculty of Health Sciences, University of Brasília, Brasília 70910-900, Brazil
    • Mariana Camargo Silva Mancini
      Mariana Camargo Silva Mancini
      Multidisciplinary Laboratory of Food and Health (LabMAS), School of Applied Sciences, University of Campinas, Campinas 13083-970, Brazil
    • Luis Gustavo Saboia Ponte
      Luis Gustavo Saboia Ponte
      Multidisciplinary Laboratory of Food and Health (LabMAS), School of Applied Sciences, University of Campinas, Campinas 13083-970, Brazil
    • Rosangela Maria Neves Bezerra
      Rosangela Maria Neves Bezerra
      Multidisciplinary Laboratory of Food and Health (LabMAS), School of Applied Sciences, University of Campinas, Campinas 13083-970, Brazil
    • Fernando Moreira Simabuco
      Fernando Moreira Simabuco
      Multidisciplinary Laboratory of Food and Health (LabMAS), School of Applied Sciences, University of Campinas, Campinas 13083-970, Brazil
    • Augusto Batagin-Neto
      Augusto Batagin-Neto
      Institute of Science and Engineering, São Paulo State University (UNESP), Itapeva, São Paulo 01049-010, Brazil
    • Guilherme Brand
      Guilherme Brand
      Laboratory for the Synthesis and Analysis of Biomolecules (LSAB), Institute of Chemistry, University of Brasilia, Brasília 70910-900, Brazil
    • Tatiana Karla S. Borges
      Tatiana Karla S. Borges
      Research Center in Morphology and Applied Immunology (NuPMIA), Faculty of Medicine, University of Brasilia, Brasília 70910-900, Brazil
    • Peter Eaton
      Peter Eaton
      LAQV/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto 4099-002, Portugal
      The Bridge, Joseph Banks Laboratories, School of Chemistry, University of Lincoln, Lincoln LN6 7TS, U.K.
      More by Peter Eaton
    • José Roberto S. A. Leite*
      José Roberto S. A. Leite
      Center for Tropical Medicine (NMT), Faculty of Medicine, University of Brasilia, Brasília 70910-900, Brazil
      Research Center in Morphology and Applied Immunology (NuPMIA), Faculty of Medicine, University of Brasilia, Brasília 70910-900, Brazil
      *Phone: +556131071891. E-mail: [email protected]; [email protected]
    Other Access OptionsSupporting Information (4)

    Journal of Natural Products

    Cite this: J. Nat. Prod. 2022, 85, 12, 2695–2705
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    https://doi.org/10.1021/acs.jnatprod.2c00304
    Published December 12, 2022
    Copyright © 2022 American Chemical Society and American Society of Pharmacognosy

    Abstract

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    In this study, we report the isolation, characterization, and synthesis of the peptide BmT-2 belonging to the tryptophyllins family, isolated from the venom of the snake Bothrops moojeni. This is the first time a tryptophyllin is identified in snake venom. We tested whether BmT-2 had cytotoxic effects and antioxidant activity in a set of experiments that included both in vitro and cell-based assays. BmT-2 presented a radical scavenging activity toward ABTS and AAPH-derived radicals. BmT-2 protected fluorescein, DNA molecules, and human red blood cells (RBCs) from free radicals generated by the thermal decomposition of AAPH. The novel tryptophyllin was not toxic in cell viability tests, where it (up to 0.4 mg/mL) did not cause hemolysis of human RBCs and did not cause significant loss of cell viability, showing a CC50 > 1.5 mM for cytotoxic effects against SK-N-BE(2) neuroblastoma cells. BmT-2 prevented the arsenite-induced upregulation of Nrf2 in Neuro-2a neuroblasts and the phorbol myristate acetate-induced overgeneration of reactive oxygen species and reactive nitrogen species in SK-N-BE(2) neuroblastoma cells. Electronic structure calculations and full atomistic reactive molecular dynamics simulations revealed the relevant contribution of aromatic residues in BmT-2 to its antioxidant properties. Our study presents a novel peptide classified into the family of the tryptophyllins, which has been reported exclusively in amphibians. Despite the promising results on its antioxidant activity and low cytotoxicity, the mechanisms of action of BmT-2 still need to be further elucidated.

    Copyright © 2022 American Chemical Society and American Society of Pharmacognosy

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.jnatprod.2c00304.

    • Video 1: Selected scenes of the molecular dynamics simulation: interaction between Phe and degraded AAPH (MPG)

    • Video 2: Selected scenes of the molecular dynamics simulation: pi–pi interaction between Phe and Trp (MPG)

    • Video 3: Selected scenes of the molecular dynamics simulation: interaction between Trp and degraded AAPH (MPG)

    • Additional information regarding molecular dynamics (PDF)

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    Cited By

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    This article is cited by 4 publications.

    1. Daiane F. Oliveira, Alex P. Coleone, Filipe C. D. A. Lima, Augusto Batagin-Neto. Reactivity of amino acids and short peptide sequences: identifying bioactive compounds via DFT calculations. Molecular Diversity 2025, 29 (1) , 489-502. https://doi.org/10.1007/s11030-024-10868-y
    2. David Meléndez-Martínez, Erika Ortega-Hernández, Edwin Estefan Reza-Zaldívar, Alejandro Carbajal-Saucedo, Gustavo Arnaud-Franco, Ana Gatica-Colima, Luis Fernando Plenge-Tellechea, Marilena Antunes-Ricardo, Daniel A. Jacobo-Velázquez, Karla Mayolo-Deloisa, Omar Lozano, Marco Rito-Palomares, Jorge Benavides. Bioprospection of rattlesnake venom peptide fractions with anti-adipose and anti-insulin resistance activity in vitro. Toxicon: X 2024, 24 , 100209. https://doi.org/10.1016/j.toxcx.2024.100209
    3. Carlos Alberto-Silva, Brenda Rufino da Silva, Julio Cezar Araujo da Silva, Felipe Assumpção da Cunha e Silva, Roberto Tadashi Kodama, Wilmar Dias da Silva, Maricilia Silva Costa, Fernanda Calheta Vieira Portaro. Small Structural Differences in Proline-Rich Decapeptides Have Specific Effects on Oxidative Stress-Induced Neurotoxicity and L-Arginine Generation by Arginosuccinate Synthase. Pharmaceuticals 2024, 17 (7) , 931. https://doi.org/10.3390/ph17070931
    4. J. Michael Conlon, Laure Guilhaudis, Samir Attoub, Laurent Coquet, Jérôme Leprince, Thierry Jouenne, Milena Mechkarska. Purification, Conformational Analysis and Cytotoxic Activities of Host-Defense Peptides from the Giant Gladiator Treefrog Boana boans (Hylidae: Hylinae). Antibiotics 2023, 12 (7) , 1102. https://doi.org/10.3390/antibiotics12071102

    Journal of Natural Products

    Cite this: J. Nat. Prod. 2022, 85, 12, 2695–2705
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.jnatprod.2c00304
    Published December 12, 2022
    Copyright © 2022 American Chemical Society and American Society of Pharmacognosy

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