Non-disulfide-bridged peptides from Tityus serrulatus venom: Evidence for proline-free ACE-inhibitors

Author(s):Show less -

Pucca, Manuela Berto ; Cerni, Felipe Augusto ; Pinheiro-Junior, Ernesto Lopes ; Zoccal, Karina Furlani ; Figueiredo Bordon, Karla de Castro ; Amorim, Fernanda Gobbi ; Peigneur, Steve ; Vriens, Kim ; Thevissen, Karin ; Angelo Cammue, Bruno Philippe ; Martins Junior, Ronaldo Braganca ; Arruda, Eurico ; Faccioli, Lucia Helena ; Tytgat, Jan ; Arantes, Eliane Candiani

• Document type: Journal article
• Source: Peptides; v. 82, p. 44-51, AUG 2016.
• Web of Science Citations: 5

Abstract

The present study purifies two T. serrulatus non-disulfide-bridged peptides (NDBPs), named venom peptides 7.2 (RLRSKG) and 8 (KIWRS) and details their synthesis and biological activity, comparing to the synthetic venom peptide 7.1 (RLRSKGKK), previously identified. The synthetic replicate peptides were subjected to a range of biological assays: hemolytic, antifungal, antiviral, electrophysiological, immunological and angiotensin-converting enzyme (ACE) inhibition activities. All venom peptides neither showed to be cytolytic nor demonstrated significant antifungal or antiviral activities. Interestingly, peptides were able to modulate macrophages' responses, increasing IL-6 production. The three venom peptides also demonstrated potential to inhibit ACE in the following order: 7.2 > 7.1 > 8. The ACE inhibition activity was unexpected, since peptides that display this function are usually proline-rich peptides. In attempt to understand the origin of such small peptides, we discovered that the isolated peptides 7.2 and 8 are fragments of the same molecule, named Pape peptide precursor. Furthermore, the study discusses that Pape fragments could be originated from a post-splitting mechanism resulting from metalloserrulases and other proteinases cleavage, which can be seen as a clever mechanism used by the scorpion to enlarge its repertoire of venom components. Scorpion venom remains as an interesting source of bioactive proteins and this study advances our knowledge about three NDBPs and their biological activities. (C) 2016 Published by Elsevier Inc. (AU)

• FAPESP's process: 13/21342-7 - Electrophysiological characterization of Ts19 fragment II, a new toxin purified from Tityus serrulatus venom
• Grantee: Felipe Augusto Cerni
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 14/03332-7 - Study of the relationship between inflammasome activation and lipid mediators production with pulmonary inflammation induced by scorpion venom with and without hyaluronidase
• Grantee: Karina Furlani Zoccal
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/13590-8 - Isolation, molecular and functional characterization of a new toxin from Tityus serrulatus scorpion venom
• Grantee: Felipe Augusto Cerni
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/06380-0 - Rhinovirus replication in explants of human tonsillar lymphoepithelial tissue infected ex vivo
• Grantee: Ronaldo Bragança Martins Júnior
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/07125-6 - New functional aspects of eicosanoids
• Grantee: Lúcia Helena Faccioli
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/21329-0 - Electrophysiological characterization of Tityus serrulatus venom toxins Ts3, Ts4, Ts6, Ts8, Ts15 and TS venom peptide 7: looking for new desired drugs
• Grantee: Manuela Berto Pucca
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 11/12317-3 - Cloning and heterologous expression of hyaluronidase and/or novel toxins obtained from the transcriptome of Tityus serrulatus' venom gland
• Grantee: Fernanda Gobbi Amorim
• Support Opportunities: Scholarships in Brazil - Doctorate