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Interactions between bioactive peptides and lipid bilayers: prizing the leishmanicidal activity

Grant number: 14/11877-3
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2014
Effective date (End): July 31, 2015
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Organic Chemistry
Principal Investigator:Marcia Perez dos Santos Cabrera
Grantee:Maira Ramos Vieira
Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil


One of the main advantages in the use of antimicrobial peptides in antibiotic therapy is the reduced chance of resistance development, since these peptides target the cell membrane phospholipid matrix. Some of these peptides are also active against Leishmania, which is the causative agent of one of the neglected diseases according to WHO. The current therapies have serious shortcomings related to toxicity, the administration forms and costs. Mechanisms of the selective action found in some bioactive peptides are investigated as a means to orient structural optimizations that can enhance the therapeutic action and at the same time minimizing toxic or undesirable side effects. Moreover studies carried out in model membranes have evidenced that features of the lipid composition of bilayers are important for selectivity and to our understanding of facts derived from this interaction. Decoralin is an undecapeptide, which in the C-terminus amidated form exhibits leishmanicidal activity towards the promastigote form of the protozoa and low cytotoxicity. Previous molecular dynamics studies comparing the structures of Decoralin and other leishmanicidal peptides suggest that some structural parameters could be responsible for this activity. This project intends to investigate the lytic activity of Decoralin and some structurally relevant analogs in experiments of leakage of a fluorescent probe from vesicles mimicking the membranes of amastigotes and of infected and non-infected macrophages. The results will be correlated to the partition coefficients in relation to the same vesicles using zeta potenctial measurements.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
LEITE, NATALIA B.; MARTINS, DANUBIA B.; FAZANI, VINICIUS E.; VIEIRA, MAIRA R.; DOS SANTOS CABRERA, MARCIA P.. Cholesterol modulates curcumin partitioning and membrane effects. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, v. 1860, n. 11, p. 2320-2328, . (14/06713-1, 14/08372-7, 14/11877-3, 12/24259-0)
MARTINS, DANUBIA BATISTA; VIEIRA, MAIRA RAMOS; FADEL, VALMIR; CAMARGO SANTANA, VIVIANE APARECIDA; RODRIGUES GUERR, MIRIAN ELISA; LIMA, MARTA LOPES; TEMPONE, ANDRE G.; DOS SANTOS CABRERA, MARCIA PEREZ. Membrane targeting peptides toward antileishmanial activity: Design, structural determination and mechanism of interaction. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, v. 1861, n. 11, A, p. 2861-2871, . (15/17331-5, 12/24259-0, 14/11877-3, 14/08372-7, 13/50228-8)

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