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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

[des-Arg(1)]-Proctolin: A novel NEP-like enzyme inhibitor identified in Tityus serrulatus venom

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Duzzi, Bruno [1] ; Cajado-Carvalho, Daniela [1] ; Kuniyoshi, Alexandre Kazuo [1] ; Kodama, Roberto Tadashi [1] ; Gozzo, Fabio Cesar [2] ; Fioramonte, Mariana [2] ; Tambourgi, Denise Vilarinho [1] ; Portaro, Fernanda Vieira [1] ; Rioli, Vanessa [3]
Total Authors: 9
[1] Butantan Inst, Immunochem Lab, Av Prof Vital Brazil 1500, BR-05503900 Sao Paulo, SP - Brazil
[2] Univ Estadual Campinas, Inst Chem, Campinas, SP - Brazil
[3] Butantan Inst, Ctr Toxins Immune Response & Cell Signaling CeTIC, Special Lab Appl Toxinol, Sao Paulo, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Peptides; v. 80, p. 18-24, JUN 2016.
Web of Science Citations: 5

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. (C) 2015 Elsevier Inc. All rights reserved. (AU)

FAPESP's process: 12/06677-0 - Study of peptidase activity of the B. jararaca venom and potential neutralizing serum produced at Instituto Butantan upon this activity: new aspects of Bothrops poisoning
Grantee:Fernanda Calheta Vieira Portaro
Support Opportunities: Regular Research Grants
FAPESP's process: 14/12976-5 - Purification and characterization of peptides present in the venom of the scorpion Tityus serrulatus
Grantee:Bruno Duzzi
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 13/15343-0 - Purification and characterization of peptidases present in the venom of the scorpion Tityus serrulatus
Grantee:Daniela Cajado de Oliveira Souza Carvalho
Support Opportunities: Scholarships in Brazil - Doctorate