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Neuroprotective effects on microglia and insights into the structure-activity relationship of an antioxidant peptide isolated from Pelophylax perezi

Title
Neuroprotective effects on microglia and insights into the structure-activity relationship of an antioxidant peptide isolated from Pelophylax perezi
Type
Article in International Scientific Journal
Year
2022
Authors
Placido, A
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do Amaral, CP
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Catia Teixeira
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Nogueira, A
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Brango Vanegas, J
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Barbosa, EA
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Moreira, DC
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Silva Carvalho, AE
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da Silva, MD
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Dias, JD
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Albuquerque, P
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Saldanha Araujo, F
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Lima, FCDA
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Batagin Neto, A
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Kuckelhaus, S
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Bessa, LJ
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Freitas, J
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Brand, GD
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Santos, NC
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Relvas, JB
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Leite, JRSA
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Eaton, P
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Journal
Vol. 26
Pages: 2793-2807
ISSN: 1582-1838
Publisher: Wiley-Blackwell
Other information
Authenticus ID: P-00W-F5C
Abstract (EN): Tryptophyllins constitute a heterogeneous group of peptides that are one of the first classes of peptides identified from amphibian's skin secretions. Here, we report the structural characterization and antioxidant properties of a novel tryptophyllin-like peptide, named PpT-2, isolated from the Iberian green frog Pelophylax perezi. The skin secretion of P. perezi was obtained by electrical stimulation and fractionated using RP-HPLC. De novo peptide sequencing was conducted using MALDI MS/MS. The primary structure of PpT-2 (FPWLLS-NH2) was confirmed by Edman degradation and subsequently investigated using in silico tools. PpT-2 shared physicochemical properties with other well-known antioxidants. To test PpT-2 for antioxidant activity in vitro, the peptide was synthesized by solid phase and assessed in the chemical-based ABTS and DPPH scavenging assays. Then, a flow cytometry experiment was conducted to assess PpT-2 antioxidant activity in oxidatively challenged murine microglial cells. As predicted by the in silico analyses, PpT-2 scavenged free radicals in vitro and suppressed the generation of reactive species in PMA-stimulated BV-2 microglia cells. We further explored possible bioactivities of PpT-2 against prostate cancer cells and bacteria, against which the peptide exerted a moderate antiproliferative effect and negligible antimicrobial activity. The biocompatibility of PpT-2 was evaluated in cytotoxicity assays and in vivo toxicity with Galleria mellonella. No toxicity was detected in cells treated with up to 512 mu g/ml and in G. mellonella treated with up to 40 mg/kg PpT-2. This novel peptide, PpT-2, stands as a promising peptide with potential therapeutic and biotechnological applications, mainly for the treatment/prevention of neurodegenerative disorders.
Language: English
Type (Professor's evaluation): Scientific
No. of pages: 15
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