Structure and in vitro activities of a Copper II-chelating anionic peptide from the venom of the scorpion Tityus stigmurus.

Autor: Melo MMA; Laboratório de Tecnologia e Biotecnologia Farmacêutica, Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN, Brazil; Programa de Pós-Graduação em Ciências Farmacêuticas, UFRN, Natal, RN, Brazil., Daniele-Silva A; Laboratório de Tecnologia e Biotecnologia Farmacêutica, Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN, Brazil., Teixeira DG; Laboratório de Sistemas Metabólicos, Centro de Biociências, UFRN, Natal, RN, Brazil., Estrela AB; Laboratório de Tecnologia e Biotecnologia Farmacêutica, Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN, Brazil., Melo KRT; Laboratório de Biotecnologia de Polímeros Naturais, UFRN, Natal, RN, Brazil., Oliveira VS; Laboratório de Química de Coordenação e Polímeros, UFRN, Natal, RN, Brazil., Rocha HAO; Laboratório de Biotecnologia de Polímeros Naturais, UFRN, Natal, RN, Brazil., Ferreira LS; Laboratório de Controle de Qualidade de Medicamentos, UFRN, Natal, RN, Brazil., Pontes DL; Laboratório de Química de Coordenação e Polímeros, UFRN, Natal, RN, Brazil., Lima JPMS; Laboratório de Sistemas Metabólicos, Centro de Biociências, UFRN, Natal, RN, Brazil., Silva-Júnior AA; Laboratório de Tecnologia e Biotecnologia Farmacêutica, Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN, Brazil; Programa de Pós-Graduação em Ciências Farmacêuticas, UFRN, Natal, RN, Brazil., Barbosa EG; Programa de Pós-Graduação em Ciências Farmacêuticas, UFRN, Natal, RN, Brazil; Laboratório de Química Farmacêutica, UFRN, Natal, RN, Brazil., Carvalho E; Centro de Biotecnologia, Instituto Butantan, São Paulo, SP, Brazil., Fernandes-Pedrosa MF; Laboratório de Tecnologia e Biotecnologia Farmacêutica, Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN, Brazil; Programa de Pós-Graduação em Ciências Farmacêuticas, UFRN, Natal, RN, Brazil. Electronic address: mpedrosa@ufrnet.br.
Jazyk: angličtina
Zdroj: Peptides [Peptides] 2017 Aug; Vol. 94, pp. 91-98. Date of Electronic Publication: 2017 May 26.
DOI: 10.1016/j.peptides.2017.05.009
Abstrakt: Anionic Peptides are molecules rich in aspartic acid (Asp) and/or glutamic acid (Glu) residues in the primary structure. This work presents, for the first time, structural characterization and biological activity assays of an anionic peptide from the venom of the scorpion Tityus stigmurus, named TanP. The three-dimensional structure of TanP was obtained by computational modeling and refined by molecular dynamic (MD) simulations. Furthermore, we have performed circular dichroism (CD) analysis to predict TanP secondary structure, and UV-vis spectroscopy to evaluate its chelating activity. CD indicated predominance of random coil conformation in aqueous medium, as well as changes in structure depending on pH and temperature. TanP has chelating activity on copper ions, which modified the peptide's secondary structure. These results were corroborated by MD data. The molar ratio of binding (TanP:copper) depends on the concentration of peptide: at lower TanP concentration, the molar ratio was 1:5 (TanP:Cu 2+ ), whereas in concentrated TanP solution, the molar ratio was 1:3 (TanP:Cu 2+ ). TanP was not cytotoxic to non-neoplastic or cancer cell lines, and showed an ability to inhibit the in vitro release of nitric oxide by LPS-stimulated macrophages. Altogether, the results suggest TanP is a promising peptide for therapeutic application as a chelating agent.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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