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    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. Copyright © 2016. Published by Elsevier Inc.

    Citation

    Manuela Berto Pucca, Felipe Augusto Cerni, Ernesto Lopes Pinheiro-Junior, Karina Furlani Zoccal, Karla de Castro Figueiredo Bordon, Fernanda Gobbi Amorim, Steve Peigneur, Kim Vriens, Karin Thevissen, Bruno Philippe Angelo Cammue, Ronaldo Bragança Martins Júnior, Eurico Arruda, Lúcia Helena Faccioli, Jan Tytgat, Eliane Candiani Arantes. Non-disulfide-bridged peptides from Tityus serrulatus venom: Evidence for proline-free ACE-inhibitors. Peptides. 2016 Aug;82:44-51

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    PMID: 27221550

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