| Grant number: | 15/25619-9 |
| Support Opportunities: | Regular Research Grants |
| Start date: | March 01, 2016 |
| End date: | February 28, 2019 |
| Field of knowledge: | Biological Sciences - Biophysics - Molecular Biophysics |
| Principal Investigator: | João Ruggiero Neto |
| Grantee: | João Ruggiero Neto |
| 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 |
| City of the host institution: | São José do Rio Preto |
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)
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