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Effect of aminophospholipids and of the pH on the interfacial activity of the anticancer peptide Polybia-MP1 and analogs in model membranes

Abstract

The antimicrobial peptide Polybia-MP1 (MP1) extracted from the native wasp Polybia paulista, revealed to be inhibitor of cancer cell proliferation besides its potent antibacterial activity. It selectively recognized leukemic T-limphocytes but not the health ones, displaying thus a potential for pharmaceutical and medical applications. We gathered strong experimental evidences indicating that the origin of this activity and selectivity is the presence of aminophospholipids phosphatidylserine (PS) and phosphatidylethanolamine (PE) in the outer leaflet of these cells. PS and PE act synergistically, PS is anionic and enhances the cationic peptide affinity and PE increases in one magnitude order the membrane permeability induced by the peptide. We have also observed that for peptides with acidic and basic residues the affinity to anionic membranes is modulated by the pH. The purpose of the present project is to investigate the biophysical-chemical bases of the synergy between PS and PE as well as the effect of small pH changes that characterize the extracellular milieu of these cells. The main focus is to understand the aspects involved in the adsorption of the peptide to the lipid bilayer and its effects on the lipid packing and on the lytic activity, and still the influences of the pH. The purpose is to use different experimental approaches that contribute to explore the synergy of these lipids and to design sequences responsive to the pH changes in the same range observed between physiologic and extracellular milieu. Hopefully, the results to be obtained will certainly contribute to the comprehension of important aspects at the interface that modulate the selectivity of these peptides contributing to the design of more selective sequences for medical applications. (AU)

Scientific publications (5)
(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)
MIASAKI, KENNETH M. F.; WILKE, NATALIA; RUGGIERO NETO, JOAO; ALVARES, DAYANE S. N-terminal acetylation of a mastoparan-like peptide enhances PE/PG segregation in model membranes. Chemistry and Physics of Lipids, v. 232, OCT 2020. Web of Science Citations: 0.
ALVARES, DAYANE S.; VIEGAS, TAISA G.; NETO, JOAO RUGGIERO. The effect of pH on the lytic activity of a synthetic mastoparan-like peptide in anionic model membranes. Chemistry and Physics of Lipids, v. 216, p. 54-64, NOV 2018. Web of Science Citations: 1.
ALVARES, DAYANE S.; WILKE, NATALIA; RUGGIERO NETO, JOAO. Effect of N-terminal acetylation on lytic activity and lipid-packing perturbation induced in model membranes by a mastoparan-like peptide. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, v. 1860, n. 3, p. 737-748, MAR 2018. Web of Science Citations: 2.
ALVARES, DAYANE S.; WILKE, NATALIA; RUGGIERO NETO, JOAO; FANANI, MARIA LAURA. The insertion of Polybia-MP1 peptide into phospholipid monolayers is regulated by its anionic nature and phase state. Chemistry and Physics of Lipids, v. 207, n. A, p. 38-48, OCT 2017. Web of Science Citations: 8.
ALVARES, DAYANE S.; RUGGIERO NETO, JOAO; AMBROGGIO, ERNESTO E. Phosphatidylserine lipids and membrane order precisely regulate the activity of Polybia-MP1 peptide. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, v. 1859, n. 6, p. 1067-1074, JUN 2017. Web of Science Citations: 4.

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