NMR three-dimensional structure of the cationic peptide Stigmurin from Tityus stigmurus scorpion venom: In vitro antioxidant and in vivo antibacterial and healing activity

• Published in: Peptides (New York, N.Y. : 1980) Vol. 137; p. 170478
• Main Authors: Daniele-Silva, Alessandra, Rodrigues, Suedson de Carvalho Silva, dos Santos, Elizabeth Cristina Gomes, Queiroz Neto, Moacir Fernandes de, Rocha, Hugo Alexandre de Oliveira, Silva-Júnior, Arnóbio Antônio da, Resende, Jarbas Magalhães, Araújo, Renata Mendonça, Fernandes-Pedrosa, Matheus de Freitas
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2021
• Subjects: Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antimicrobial; Antimicrobial Cationic Peptides - pharmacology; Antioxidant activity; Antioxidants - chemistry; Antioxidants - pharmacology; Humans; Magnetic Resonance Spectroscopy; NMR structure; Protein Conformation; Scorpion venom; Scorpion Venoms - chemistry; Scorpion Venoms - genetics; Scorpions - chemistry; Staphylococcus aureus - drug effects; Staphylococcus aureus - pathogenicity; Wound Infection - drug therapy; Wound Infection - microbiology; Antimicrobial; NMR structure; Scorpion venom; Antioxidant activity
• DOI: 10.1016/j.peptides.2020.170478
• ISSN: 0196-9781

[Display omitted] •Stigmurin showed high hydroxyl radical scavenging activity in vitro.•Stigmurin revelad antibiotic effect in the model of skin wound infection.•Stigmurin increased the retraction rate of the skin lesion in vivo.•Stigmurin showed an amphipathic helical structure with a flexible N-terminus region. Infectious diseases and the rapid development of pathogens resistant to conventional drugs are a serious global public health problem, which motivates the search for new pharmacological agents. In this context, cationic peptides without disulfide bridges from different species of scorpion venom have been the target of scientific studies due to their multifunctional activities. Stigmurin is a linear peptide composed of 17 amino acid residues (Phe-Phe-Ser-Leu-Ile-Pro-Ser-Leu-Val-Gly-Gly-Leu-Ile-Ser-Ala-Phe-Lys-NH2), which is present in the venom gland of the scorpion Tityus stigmurus. Here we present investigations of the in vitro antioxidant action of Stigmurin together with the in vivo antibacterial and healing activity of this peptide in a wound infection model induced by Staphylococcus aureus. In addition, we have reports for the first time of the three-dimensional structure determined by NMR spectroscopy of a peptide without disulfide bridges present in scorpion venom from the Tityus genus. Stigmurin showed hydroxyl radical scavenging above 70 % at 10 μM and antibiotic action in the skin wound, reducing the number of viable microorganisms by 67.2 % on the 7 day after infection. Stigmurin (1 μg / μL) increased the retraction rate of the lesion, with wound area reduction of 43 % on the second day after skin injury, which indicates its ability to induce tissue repair. Stigmurin in trifluoroethanol:water exhibited a random conformation at the N-terminus region (Phe1 to Pro6), with a helical structure from Ser7 to Phe16. This structural information, allied with the multifunctional activity of Stigmurin, makes it an attractive candidate for the design of novel therapeutic agents.