Rational design of a trypanocidal peptide derived from Dinoponera quadriceps venom.

Fecha de publicación: 05/11/2022

Autores de CIPF

Maria Mar Orzáez Calatayud

Autor

Participantes ajenos a CIPF

Monteiro ML
Lima DB
Freire KA
Nicolaski Pedron C
Magalhães EP
Silva BP
García-Jareño AB
De Oliveira CS
Nunes JVS
Marinho MM
Menezes RRPPB
Oliveira Junior VX
Martins AMC

Grupos de Investigación

Laboratorio de Terapias Dirigidas en Cáncer e Inflamación

Jefe/a de Grupo

Maria Mar Orzáez Calatayud

Abstract

Chagas disease is caused by the parasite Trypanosoma cruzi and affects millions of people worldwide, having no effective cure. The main sanitary emergency is related to patients with chronic infection, which accumulate comorbidities causing patient death. However, actual chemotherapeutic treatments do not effectively address the chronic forms of the disease. Invertebrates are a relevant source of antimicrobial peptides (AMPs) as part of the innate immune system for their protection. The AMP M-PONTX-Dq3a, isolated from the Dinoponera quadriceps ant venom, has shown very effective antimicrobial and trypanocidal activities. Although M-PONTX-Dq3a has better activity that the current therapies, the peptide length has limited its possibilities to reach clinical application. In this investigation, we aimed to dissect the trypanocidal effect of M-PONTX-Dq3a fragments and to study the activity of substituted analogs, to improve not only peptide trypanocidal activity and bioavailability, but also production costs. Our studies have led to the identification of two smaller peptides, M-PONTX-Dq3a [1-15] and [Lys] 3 -M-PONTX-Dq3a [3-153-15 with similar trypanocidal activities that the parent peptide has against the three forms of T. cruzi benznidazole-resistant Y strain. Both peptides represent promising candidates to develop novel and effective trypanocidal bio-therapeutic agents, opening new avenues for the treatment of chronic patients.

Datos de la publicación

ISSN/ISSNe:: 0223-5234, 1768-3254
Tipo:: Article
Páginas:: 114624-114624
DOI:: 10.1016/j.ejmech.2022.114624
PubMed:: 35933786

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Métricas

Filiaciones

Monteiro ML:: Department of Clinical and Toxicological Analysis, Faculdade de Farmácia, Universidade Federal do Ceará, Fortaleza, 60430372, CE, Brazil
Lima DB:: Department of Clinical and Toxicological Analysis, Faculdade de Farmácia, Universidade Federal do Ceará, Fortaleza, 60430372, CE, Brazil
Freire KA:: Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, 09210580, SP, Brazil
Nicolaski Pedron C:: Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, 09210580, SP, Brazil
Magalhães EP:: Department of Clinical and Toxicological Analysis, Faculdade de Farmácia, Universidade Federal do Ceará, Fortaleza, 60430372, CE, Brazil
Silva BP:: Department of Clinical and Toxicological Analysis, Faculdade de Farmácia, Universidade Federal do Ceará, Fortaleza, 60430372, CE, Brazil
García-Jareño AB:: Targeted Therapies on Cancer and Inflammation Lab and Peptide Synthesis Platform, Centro de Investigación Príncipe Felipe, Valencia, 46012, Spain
De Oliveira CS:: Department of Biophysics, Universidade Federal de São Paulo, São Paulo, SP, 04044020, Brazil
Nunes JVS:: Department of Clinical and Toxicological Analysis, Faculdade de Farmácia, Universidade Federal do Ceará, Fortaleza, 60430372, CE, Brazil
Marinho MM:: Department of Clinical and Toxicological Analysis, Faculdade de Farmácia, Universidade Federal do Ceará, Fortaleza, 60430372, CE, Brazil
Menezes RRPPB:: Department of Clinical and Toxicological Analysis, Faculdade de Farmácia, Universidade Federal do Ceará, Fortaleza, 60430372, CE, Brazil
Orzaéz M:: Targeted Therapies on Cancer and Inflammation Lab and Peptide Synthesis Platform, Centro de Investigación Príncipe Felipe, Valencia, 46012, Spain
Oliveira Junior VX:: Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, 09210580, SP, Brazil

Department of Biophysics, Universidade Federal de São Paulo, São Paulo, SP, 04044020, Brazil
Martins AMC:: Department of Clinical and Toxicological Analysis, Faculdade de Farmácia, Universidade Federal do Ceará, Fortaleza, 60430372, CE, Brazil