A novel metalloproteinase-derived cryptide from Bothrops cotiara venom inhibits angiotensin-converting enzyme activity

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Miyamoto, Jackson Gabriel ; Kitano, Eduardo Shigueo ; Zelanis, Andre ; Nachtigall, Pedro Gabriel ; Junqueira-de-Azevedo, Inacio ; Sant'Anna, Savio Stefanini ; Silva, Rogerio Lauria da ; Bersanetti, Patricia Alessandra ; Carmona, Adriana Karaoglanovic ; Pereira, Pedro Jose Barbosa ; Serrano, Solange M. T. ; Oliva, Maria Luiza Vilela ; Tashima, Alexandre Keiji

• Document type: Journal article
• Source: Biochimie; v. 216, p. 9-pg., 2023-11-21.

Abstract

Snake venoms are primarily composed of proteins and peptides, which selectively interact with specific molecular targets, disrupting prey homeostasis. Identifying toxins and the mechanisms involved in envenoming can lead to the discovery of new drugs based on natural peptide scaffolds. In this study, we used mass spectrometry-based peptidomics to sequence 197 peptides in the venom of Bothrops cotiara, including a novel 7-residue peptide derived from a snake venom metalloproteinase. This peptide, named Bc-7a, features a pyroglutamic acid at the N-terminal and a PFR motif at the C-terminal, homologous to bradykinin. Using FRET (fluorescence resonance energy transfer) substrate assays, we demonstrated that Bc-7a strongly inhibits the two domains of angiotensin converting enzyme (K-i < 1 mM). Our findings contribute to the repertoire of biologically active peptides from snake venoms capable of inhibiting angiotensin-converting enzyme (ACE), beyond current known structural motifs and precursors. In summary, we report a novel snake venom peptide with ACE inhibitory activity, suggesting its potential contribution to the hypotensive effect observed in envenomation. (c) 2023 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved. (AU)

• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 17/21052-0 - Sepsis: mechanisms, therapeutic targets and epidemiology
• Grantee: Reinaldo Salomão
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 21/05975-6 - Anti-SARS-CoV-2 antibodies in the plasma of vaccinees: dynamics of humoral response, sequencing, expression and effectiveness of recombinants for therapy and diagnosis
• Grantee: Alexandre Keiji Tashima
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/20106-9 - Peptidomics of Brazilian snake and spider venoms
• Grantee: Alexandre Keiji Tashima
• Support Opportunities: Regular Research Grants