title: [des-Arg(1)]-Proctolin: A novel NEP-like enzyme inhibitor identified in Tityus serrulatus venom.
abstract: The scorpion Tityus serrulatus venom comprises a complex mixture of molecules that paralyzes and kills preys, especially insects. However, venom components also interact with molecules in humans, causing clinic envenomation. This cross-interaction may result from homologous molecular targets in mammalians and insects, such as (NEP)-like enzymes. In face of these similarities, we searched for peptides in Tityus serrulatus venom using human NEP as a screening tool. We found a NEP-inhibiting peptide with the primary sequence YLPT, which is very similar to that of the insect neuropeptide proctolin (RYLPT). Thus, we named the new peptide [des-Arg(1)]-proctolin. Comparative NEP activity assays using natural substrates demonstrated that [des-Arg(1)]-proctolin has high specificity for NEP and better inhibitory activity than proctolin. To test the initial hypothesis that molecular homologies allow Tityus serrulatus venom to act on both mammal and insect targets, we investigated the presence of a NEP-like in cockroaches, the main scorpion prey, that could be likewise inhibited by [des-Arg(1)]-proctolin. Indeed, we detected a possible NEP-like in a homogenate of cockroach heads whose activity was blocked by thiorphan and also by [des-Arg(1)]-proctolin. Western blot analysis using a human NEP monoclonal antibody suggested a NEP-like enzyme in the homogenate of cockroach heads. Our study describes for the first time a proctolin-like peptide, named [des-Arg(1)]-proctolin, isolated from Tityus serrulatus venom. The tetrapeptide inhibits human NEP activity and a NEP-like activity in a cockroach head homogenate, thus it may play a role in human envenomation as well as in the paralysis and death of scorpion preys.
authors.affiliation: Immunochemistry Laboratory, Butantan Institute, Av. Prof. Vital Brazil, 1500, CEP 05503-900, São Paulo, SP, Brazil.
authors.forename: Bruno
authors.initials: B
authors.lastname: Duzzi
authors.affiliation: Immunochemistry Laboratory, Butantan Institute, Av. Prof. Vital Brazil, 1500, CEP 05503-900, São Paulo, SP, Brazil.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cajado-Carvalho
authors.affiliation: Immunochemistry Laboratory, Butantan Institute, Av. Prof. Vital Brazil, 1500, CEP 05503-900, São Paulo, SP, Brazil.
authors.forename: Alexandre Kazuo
authors.initials: AK
authors.lastname: Kuniyoshi
authors.affiliation: Immunochemistry Laboratory, Butantan Institute, Av. Prof. Vital Brazil, 1500, CEP 05503-900, São Paulo, SP, Brazil.
authors.forename: Roberto Tadashi
authors.initials: RT
authors.lastname: Kodama
authors.affiliation: Chemistry Institute, University of Campinas, Campinas, SP, Brazil.
authors.forename: Fabio Cesar
authors.initials: FC
authors.lastname: Gozzo
authors.affiliation: Chemistry Institute, University of Campinas, Campinas, SP, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Fioramonte
authors.affiliation: Immunochemistry Laboratory, Butantan Institute, Av. Prof. Vital Brazil, 1500, CEP 05503-900, São Paulo, SP, Brazil.
authors.forename: Denise Vilarinho
authors.initials: DV
authors.lastname: Tambourgi
authors.affiliation: Immunochemistry Laboratory, Butantan Institute, Av. Prof. Vital Brazil, 1500, CEP 05503-900, São Paulo, SP, Brazil. Electronic address: fernanda.portaro@butantan.gov.br.
authors.forename: Fernanda Vieira
authors.initials: FV
authors.lastname: Portaro
authors.affiliation: Special Laboratory of Applied Toxinology/Center of Toxins, Immune-Response and Cell Signaling (CeTICS), Butantan Institute, São Paulo, SP, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Rioli
mesh_terms: D000818:Animals; D006801:Humans; D015153:Blotting, Western; D003058:Cockroaches / Q000201:enzymology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006257:Head; D006868:Hydrolysis; D015260:Neprilysin / Q000037:antagonists & inhibitors; D009479:Neuropeptides / Q000737:chemistry / Q000494:pharmacology; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D012604:Scorpion Venoms / Q000737:chemistry; D012605:Scorpions / Q000737:chemistry; D015244:Thiorphan / Q000494:pharmacology
chemical_list: C000614677:(des-Arg1)-proctolin; D004791:Enzyme Inhibitors; D015260:Neprilysin; D009479:Neuropeptides; D009842:Oligopeptides; C011536:proctolin; D012604:Scorpion Venoms; D015244:Thiorphan
keywords: Cockroach; Neprilysin (NEP); Neuropeptide; Proctolin; Scorpion venom; Tityus serrulatus; [des-Arg(1)]-proctolin