title: Non-disulfide-bridged peptides from Tityus serrulatus venom: Evidence for proline-free ACE-inhibitors.
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.
authors.affiliation: Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Manuela Berto
authors.initials: MB
authors.lastname: Pucca
authors.affiliation: Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Felipe Augusto
authors.initials: FA
authors.lastname: Cerni
authors.affiliation: Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Ernesto Lopes
authors.initials: EL
authors.lastname: Pinheiro-Junior
authors.affiliation: Department of Clinical Analysis, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Karina Furlani
authors.initials: KF
authors.lastname: Zoccal
authors.affiliation: Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Karla de Castro Figueiredo
authors.initials: KCF
authors.lastname: Bordon
authors.affiliation: Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Fernanda Gobbi
authors.initials: FG
authors.lastname: Amorim
authors.affiliation: Toxicology and Pharmacology, University of Leuven, Leuven, Belgium.
authors.forename: Steve
authors.initials: S
authors.lastname: Peigneur
authors.affiliation: Centre of Microbial and Plant Genetics, University of Leuven, Heverlee, Belgium.
authors.forename: Kim
authors.initials: K
authors.lastname: Vriens
authors.affiliation: Centre of Microbial and Plant Genetics, University of Leuven, Heverlee, Belgium.
authors.forename: Karin
authors.initials: K
authors.lastname: Thevissen
authors.affiliation: Centre of Microbial and Plant Genetics, University of Leuven, Heverlee, Belgium; Department of Plant Systems Biology, VIB, Technologiepark 927, 9052 Gent, Belgium.
authors.forename: Bruno Philippe Angelo
authors.initials: BPA
authors.lastname: Cammue
authors.affiliation: Department of Cell Biology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Ronaldo Bragança Martins
authors.initials: RBM
authors.lastname: Júnior
authors.affiliation: Department of Cell Biology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Eurico
authors.initials: E
authors.lastname: Arruda
authors.affiliation: Department of Clinical Analysis, Toxicology and Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Lúcia Helena
authors.initials: LH
authors.lastname: Faccioli
authors.affiliation: Toxicology and Pharmacology, University of Leuven, Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Tytgat
authors.affiliation: Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: ecabraga@fcfrp.usp.br.
authors.forename: Eliane Candiani
authors.initials: EC
authors.lastname: Arantes
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification*; D000818:Animals; D004220:Disulfides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry / Q000378:metabolism*; D011392:Proline / Q000737:chemistry; D012604:Scorpion Venoms / Q000737:chemistry* / Q000378:metabolism; D012605:Scorpions / Q000737:chemistry / Q000235:genetics
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004220:Disulfides; D010455:Peptides; D012604:Scorpion Venoms; D011392:Proline; D007703:Peptidyl-Dipeptidase A
keywords: Angiotensin-converting enzyme; Bradykinin potentiating activities; Linear peptides; Scorpion venom; Toxin