Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Potential use of 13-mer peptides based on phospholipase and oligoarginine as leishmanicidal agents

Full text
Author(s):
Mendes, Bruno [1] ; Almeida, Jose R. [2] ; Vale, Nuno [3, 4] ; Gomes, Paula [5] ; Gadelha, Fernanda R. [6] ; Da Silva, Saulo L. [7, 8] ; Miguel, Danilo C. [1]
Total Authors: 7
Affiliation:
[1] Univ Estadual Campinas UNICAMP, Inst Biol, Dept Biol Anim, Campinas, SP - Brazil
[2] Univ Reg Amazon Ikiam, Km 7 Via Muyuna, Tena, Napo - Ecuador
[3] Univ Porto, Fac Farm, Dept Ciencias Medicamento, Lab Farmacol, Porto - Portugal
[4] Univ Porto, IPATIMUP Inst Invest & Inovacao Saude I3S, Porto - Portugal
[5] Univ Porto, Fac Ciencias, Dept Quim & Bioquim, LAQV REQUIMTE, Porto - Portugal
[6] Univ Estadual Campinas Unicamp, Inst Biol, Dept Bioquim & Biol Tecidual, Campinas, SP - Brazil
[7] Univ Cuenca, Fac Ciencias Quim, Cuenca Azuay - Ecuador
[8] Ctr Innovac Salud EUS EP, Cuenca Azuay - Ecuador
Total Affiliations: 8
Document type: Journal article
Source: COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY; v. 226, DEC 2019.
Web of Science Citations: 0
Abstract

Phospholipase A(2) toxins present in snake venoms interact with biological membranes and serve as structural models for the design of small peptides with anticancer, antibacterial and antiparasitic properties. Oligoarginine peptides are capable of increasing cell membrane permeability (cell penetrating peptides), and for this reason are interesting delivery systems for compounds of pharmacological interest. Inspired by these two families of bioactive molecules, we have synthesized two 13-mer peptides as potential antileishmanial leads gaining insights into structural features useful for the future design of more potent peptides. The peptides included p-Acl, reproducing a natural segment of a Lys49 PLA(2) from Agkistrodon contortrix laticinctus snake venom, and its p-AclR7 analogue where all seven lysine residues were replaced by arginines. Both peptides were active against promastigote and amastigote forms of Leishmania (L.) amazonensis and L. (L.) infantum, while displaying low cytotoxicity for primary murine macrophages. Spectrofluorimetric studies suggest that permeabilization of the parasite's cell membrane is the probable mechanism of action of these biomolecules. Relevantly, the engineered peptide p-AclR7 was more active in both life stages of Leishmania and induced higher rates of ethidium bromide incorporation than its native template p-Acl. Taken together, the results suggest that short peptides based on phospholipase toxins are potential scaffolds for development of antileishmanial candidates. Moreover, specific amino acid substitutions, such those herein employed, may enhance the antiparasitic action of these cationic peptides, encouraging their future biomedical applications. (AU)

FAPESP's process: 14/21129-4 - The role of fatty acid-binding proteins in the macrophage infection by Leishmania: a potential target for new drugs against leishmaniasis
Grantee:Danilo Ciccone Miguel
Support Opportunities: Research Grants - Young Investigators Grants