TanP: A Multifunctional Anionic Peptide From Tityus stigmurus Scorpion Venom

Menilla Maria Alves de Melo; Verônica da Silva Oliveira; Moacir Fernandes de Queiroz Neto; Weslley de Souza Paiva; Manoela Torres-Rêgo; Sérgio Ruschi Bergamachi Silva; Daniel de Lima Pontes; Hugo Alexandre Oliveira Rocha; Miguel Ângelo Fonseca de Souza; Arnóbio Antônio da Silva-Júnior; Matheus de Freitas Fernandes-Pedrosa

doi:10.3389/fmolb.2021.785316

TanP: A Multifunctional Anionic Peptide From Tityus stigmurus Scorpion Venom

Front Mol Biosci. 2022 Jan 17:8:785316. doi: 10.3389/fmolb.2021.785316. eCollection 2021.

Affiliations

¹ Laboratory of Pharmaceutical Technology and Biotechnology, Department of Pharmacy, Federal University of Rio Grande do Norte, Natal, Brazil.
² Laboratory of Coordination Chemistry and Polymers, Institute of Chemistry, Federal University of Rio Grande do Norte, Natal, Brazil.
³ Laboratory of Natural Polymer Biotechnology, Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, Brazil.
⁴ Laboratory of Synthesis and Isolation of Organic Compounds, Chemistry Institute, Federal University of Rio Grande do Norte, Natal, Brazil.
⁵ Institute of Brain, Federal University of Rio Grande do Norte, Natal, Brazil.
⁶ Laboratory of Computational Chemistry, Institute of Chemistry, Federal University of Rio Grande do Norte, Natal, Brazil.

Abstract

Anionic peptides of scorpions are molecules rich in aspartic and/or glutamic acid residues and correspond to a class of peptides without disulfide bonds that are still little explored. TanP is a linear anionic peptide (50 amino acid residues and net charge -20) present in the venom gland of the scorpion, Tityus stigmurus, with chelating properties for Cu²⁺ ion and immunomodulatory properties. The therapeutic application of chelating molecules is related to cases of acute or chronic intoxication by metals, neurodegenerative diseases, hematological diseases, healing of skin wounds, cardiovascular diseases, and cancer. In this approach, the chelating activity of TanP was evaluated in relation to new metal ions (Fe²⁺ and Zn²⁺) of biological importance, as well as its antioxidant, hemostatic, immunomodulatory, and healing potential, aiming to expand the biological and biotechnological potential of this peptide. TanP (25 µM) was able to form stable complexes with Fe²⁺ in a ratio of 1:5 (TanP: Fe²⁺). Theoretical results suggest that TanP can work as a sensor to identify and quantify Fe²⁺ ions. The fluorescence intensity of TanP (1.12 µM) decreased significantly after the addition of Fe²⁺, obtaining the highest ratio 1: 7.4 (TanP: Fe²⁺) that led to the lowest fluorescence intensity. For Zn²⁺, no relevant spectral change was noted. TanP (50 µM) showed a maximum of 3% of hemolytic activity, demonstrating biocompatibility, as well as exhibiting a 1,1-diphenyl-2-picrylhydrazyl radical-scavenging activity of above 70% at all the concentrations tested (1-25 μM), and 89.7% iron-chelating activity at 25 μM and 96% hydroxyl radical-scavenging activity at 73.6 μM. In addition, TanP (12.5 and 25 µM) revealed an anticoagulant effect, prolonging the clotting time in prothrombin time and activated partial thromboplastin time assays, with no fibrinogenolytic activity. TanP (12.5 and 25 µM) induced the release of TNF-α by murine macrophages, in the absence of lipopolysaccharides, with a concentration-dependent increase and also stimulated the migration of 3T3 cells in the in vitro healing assay. Thus, TanP revealed a multifunctional potential, being useful as a prototype for the development of new therapeutic and biotechnological agents.

Keywords: Tityus stigmurus scorpion; anionic peptide; antioxidant; chelating; immunomodulatory.